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15182647 | [Correlation between activation-induced cytidine deaminase gene polymorphism and atopic asthma and plasma IgE in adult]. | AIM: To explore whether the activation-induced cytidine deaminase(AICDA) gene 8408 C/T polymorphism is related to adult atopic asthma and the level of plasma IgE. METHODS: The polymorphism of AICDA gene was detected by PCR and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of 8408T/T genotype had significant difference (P<0.05) between adult asthma patients and control group, while the frequencies of T allele between two groups were not significantly different. The total plasma IgE level in adult atopic asthma patients with 8408T/T genotype was higher than that in the patients with C/C and C/T genotypes(P<0.05). CONCLUSION: The 8408 T/T genotype of AICDA is correlated with atopic asthma and total plasma IgE level in adult. | [Correlation between /"activation-induced cytidine deaminase"/ gene polymorphism and atopic asthma and plasma IgE in adult]. | AIM: To explore whether the /"activation-induced cytidine deaminase"/(/"AICDA"/) gene 8408 C/T polymorphism is related to adult atopic asthma and the level of plasma IgE. METHODS: The polymorphism of /"AICDA"/ gene was detected by PCR and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of 8408T/T genotype had significant difference (P<0.05) between adult /"asthma"/ patients and control group, while the frequencies of T allele between two groups were not significantly different. The total plasma IgE level in adult atopic asthma patients with 8408T/T genotype was higher than that in the patients with C/C and C/T genotypes(P<0.05). CONCLUSION: The 8408 T/T genotype of /"AICDA"/ is correlated with atopic asthma and total plasma IgE level in adult. | [
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15182647 | [Correlation between activation-induced cytidine deaminase gene polymorphism and atopic asthma and plasma IgE in adult]. | AIM: To explore whether the activation-induced cytidine deaminase(AICDA) gene 8408 C/T polymorphism is related to adult atopic asthma and the level of plasma IgE. METHODS: The polymorphism of AICDA gene was detected by PCR and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of 8408T/T genotype had significant difference (P<0.05) between adult asthma patients and control group, while the frequencies of T allele between two groups were not significantly different. The total plasma IgE level in adult atopic asthma patients with 8408T/T genotype was higher than that in the patients with C/C and C/T genotypes(P<0.05). CONCLUSION: The 8408 T/T genotype of AICDA is correlated with atopic asthma and total plasma IgE level in adult. | [Correlation between /"activation-induced cytidine deaminase"/ gene polymorphism and /"atopic asthma"/ and plasma IgE in adult]. | AIM: To explore whether the /"activation-induced cytidine deaminase"/(/"AICDA"/) gene 8408 C/T polymorphism is related to adult /"atopic asthma"/ and the level of plasma IgE. METHODS: The polymorphism of /"AICDA"/ gene was detected by PCR and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of 8408T/T genotype had significant difference (P<0.05) between adult asthma patients and control group, while the frequencies of T allele between two groups were not significantly different. The total plasma IgE level in adult /"atopic asthma"/ patients with 8408T/T genotype was higher than that in the patients with C/C and C/T genotypes(P<0.05). CONCLUSION: The 8408 T/T genotype of /"AICDA"/ is correlated with /"atopic asthma"/ and total plasma IgE level in adult. | [
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15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of /"heart failure"/. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and /"interferon (IFN)-gamma"/ cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and /"IFN-gamma"/ plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and /"IFN-gamma"/ at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but /"IFN-gamma"/ polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | [
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15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: /"Tumor necrosis factor"/ (/"TNF)-alpha"/ has been implicated in the pathophysiology of /"heart failure"/. We explored a possible association between /"TNF-alpha"/, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: /"TNF-alpha"/, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of /"TNF-alpha"/ within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma /"TNF-alpha"/ levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | [
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15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of /"heart failure"/. We explored a possible association between TNF-alpha, interleukin (IL)-6, /"IL-10"/, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, /"IL-10"/, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, /"IL-10"/ within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | [
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} | Yes |
15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of /"heart failure"/. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, /"TGF-beta1"/, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, /"TGF-beta1"/ at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but /"TGF-beta1"/ levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | [
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} | Yes |
15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of /"heart failure"/. We explored a possible association between TNF-alpha, /"interleukin (IL)-6"/, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, /"IL-6"/, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, /"IL-6"/ within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | [
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15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in /"cardiogenic shock"/. | STUDY OBJECTIVES: /"Tumor necrosis factor"/ (/"TNF)-alpha"/ has been implicated in the pathophysiology of heart failure. We explored a possible association between /"TNF-alpha"/, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from /"cardiogenic shock"/. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with /"cardiogenic shock"/ of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: /"TNF-alpha"/, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of /"TNF-alpha"/ within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma /"TNF-alpha"/ levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with /"cardiogenic shock"/ and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the /"cardiogenic shock"/ group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of /"cardiogenic shock"/ but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, /"cardiogenic shock"/. | [
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15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in /"cardiogenic shock"/. | STUDY OBJECTIVES: /"Tumor necrosis factor"/ (/"TNF)-alpha"/ has been implicated in the pathophysiology of heart failure. We explored a possible association between /"TNF-alpha"/, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from /"cardiogenic shock"/. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with /"cardiogenic shock"/ of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: /"TNF-alpha"/, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of /"TNF-alpha"/ within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma /"TNF-alpha"/ levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with /"cardiogenic shock"/ and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the /"cardiogenic shock"/ group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of /"cardiogenic shock"/ but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, /"cardiogenic shock"/. | [
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15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in /"cardiogenic shock"/. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and /"interferon (IFN)-gamma"/ cytokine polymorphisms, their in vivo production, and mortality from /"cardiogenic shock"/. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with /"cardiogenic shock"/ of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and /"IFN-gamma"/ plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and /"IFN-gamma"/ at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with /"cardiogenic shock"/ and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but /"IFN-gamma"/ polymorphism was less common in the /"cardiogenic shock"/ group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of /"cardiogenic shock"/ but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, /"cardiogenic shock"/. | [
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15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in /"cardiogenic shock"/. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, /"IL-10"/, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from /"cardiogenic shock"/. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with /"cardiogenic shock"/ of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, /"IL-10"/, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, /"IL-10"/ within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with /"cardiogenic shock"/ and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the /"cardiogenic shock"/ group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of /"cardiogenic shock"/ but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, /"cardiogenic shock"/. | [
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} | No |
15189946 | Association between the TNF-2 allele and a better survival in cardiogenic shock. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, TGF-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the cardiogenic shock group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock. | Association between the TNF-2 allele and a better survival in /"cardiogenic shock"/. | STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma cytokine polymorphisms, their in vivo production, and mortality from /"cardiogenic shock"/. DESIGN: Prospective, observational study. SETTING: Thirty-one bed, university, medicosurgical department of intensive care. PATIENTS: Thirty-three adult patients with /"cardiogenic shock"/ of recent (< 4 h) onset. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: TNF-alpha, IL-6, IL-10, /"TGF-beta1"/, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha within the promoter at position -308a-->g, IL-6 within the promoter at position -174c-->g, IL-10 within the promoter at position -1082a-->g/-819t-->c and -819t-->c/-592a-->c, /"TGF-beta1"/ at codon 10t-->c and codon 25c-->g, and IFN-gamma at intron 1 at position + 874t-->a were studied. The 33 patients had a mean (+/- SD) age of 64 +/- 17 years and a mean simplified acute physiology score II of 62.3 +/- 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-alpha levels between the TNF-1 and the TNF-2 groups, but /"TGF-beta1"/ levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with /"cardiogenic shock"/ and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-gamma polymorphism was less common in the /"cardiogenic shock"/ group (p = 0.034). CONCLUSIONS: Patients with the TNF-2 allele have no greater risk of /"cardiogenic shock"/ but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, /"cardiogenic shock"/. | [
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15190266 | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-/"IL1RN"/ gene cluster: association with /"knee osteoarthritis"/. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-/"IL1RN"/ gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-/"IL1RN"/ cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-/"IL1RN"/ complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-/"IL1RN"/ haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-/"IL1RN"/ haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-/"IL1RN"/ haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | [
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15190266 | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | Extended haplotypes and linkage disequilibrium in the IL1R1-/"IL1A"/-IL1B-IL1RN gene cluster: association with /"knee osteoarthritis"/. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the /"IL1A"/-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the /"IL1A"/-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the /"IL1A"/-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk /"IL1A"/-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | [
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15190266 | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | Extended haplotypes and linkage disequilibrium in the /"IL1R1"/-IL1A-IL1B-IL1RN gene cluster: association with /"knee osteoarthritis"/. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the /"IL1R1"/ promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the /"IL1R1"/ exon 1A region. We found limited LD between /"IL1R1"/ and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. /"IL1R1"/ promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | [
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15190266 | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-/"IL1B"/-IL1RN gene cluster: association with /"knee osteoarthritis"/. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-/"IL1B"/-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-/"IL1B"/-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-/"IL1B"/-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one /"IL1B"/-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-/"IL1B"/-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective /"IL1B"/-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | [
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15190266 | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | Extended haplotypes and linkage disequilibrium in the /"IL1R1"/-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the /"IL1R1"/ promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with /"osteoarthritis"/ (/"OA"/), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the /"IL1R1"/ exon 1A region. We found limited LD between /"IL1R1"/ and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee /"OA"/, we genotyped 141 patients from Bristol (UK) at the 17 loci. /"IL1R1"/ promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of /"OA"/ (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee /"OA"/ patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of /"OA"/ (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of /"OA"/ (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and /"OA"/. | [
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15190266 | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | Extended haplotypes and linkage disequilibrium in the /"IL1R1"/-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the /"IL1R1"/ promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with /"osteoarthritis"/ (/"OA"/), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the /"IL1R1"/ exon 1A region. We found limited LD between /"IL1R1"/ and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee /"OA"/, we genotyped 141 patients from Bristol (UK) at the 17 loci. /"IL1R1"/ promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of /"OA"/ (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee /"OA"/ patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of /"OA"/ (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of /"OA"/ (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and /"OA"/. | [
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15190266 | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | Extended haplotypes and linkage disequilibrium in the IL1R1-/"IL1A"/-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the /"IL1A"/-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with /"low-level inflammation"/. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the /"IL1A"/-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the /"IL1A"/-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk /"IL1A"/-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | [
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15190266 | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. | Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-/"IL1RN"/ gene cluster: association with knee osteoarthritis. | The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-/"IL1RN"/ gene complex, and their association with /"osteoarthritis"/ (/"OA"/), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-/"IL1RN"/ cluster, although LD within these two individual groups was high. To test association with knee /"OA"/, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-/"IL1RN"/ complex, we identified a common haplotype conferring a four-fold risk of /"OA"/ (P=0.00043; Pc=0.0043) and one IL1B-/"IL1RN"/ haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee /"OA"/ patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-/"IL1RN"/ haplotype conferred a two-fold risk of /"OA"/ (P=0.02), and the protective IL1B-/"IL1RN"/ haplotype conferred a five-fold reduced risk of /"OA"/ (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and /"OA"/. | [
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15191797 | Reciprocal changes of CD44 and GAP-43 expression in the dentate gyrus inner molecular layer after status epilepticus in mice. | Mossy fiber sprouting (MFS), a common feature of human temporal lobe epilepsy and many epilepsy animal models, contributes to hippocampal hyperexcitability. The molecular events responsible for MFS are not well understood, although the growth-associated protein GAP-43 has been implicated in rats. Here, we focus on the hyaluronan receptor CD44, which is involved in routing of retinal axons during development and is upregulated after injury in many tissues including brain. After pilocarpine-induced status epilepticus (SE) in mice most hilar neurons died and neuropeptide Y (NPY) immunoreactivity appeared in the dentate inner molecular layer (IML) after 10-31 days indicative of MFS. Strong CD44 immunoreactivity appeared in the IML 3 days after pilocarpine, then declined over the next 4 weeks. Conversely, GAP-43 immunoreactivity was decreased in the IML at 3-10 days after pilocarpine-induced SE. After SE induced by repeated kainate injections, mice did not show any hilar cell loss or changes in CD44 or GAP-43 expression in the IML, and MFS was absent at 20-35 days. Thus, after SE in mice, early loss of GAP-43 and strong CD44 induction in the IML correlated with hilar cell loss and subsequent MFS. CD44 is one of the earliest proteins upregulated in the IML and coincides with early sprouting of mossy fibers, although its function is still unknown. We hypothesize that CD44 is involved in the response to axon terminal degeneration and/or neuronal reorganization preceding MFS. | Reciprocal changes of /"CD44"/ and GAP-43 expression in the dentate gyrus inner molecular layer after status epilepticus in mice. | Mossy fiber sprouting (MFS), a common feature of human temporal lobe epilepsy and many epilepsy animal models, contributes to hippocampal hyperexcitability. The molecular events responsible for MFS are not well understood, although the growth-associated protein GAP-43 has been implicated in rats. Here, we focus on the hyaluronan receptor /"CD44"/, which is involved in routing of retinal axons during development and is upregulated after injury in many tissues including brain. After pilocarpine-induced status epilepticus (SE) in mice most hilar neurons died and neuropeptide Y (NPY) immunoreactivity appeared in the dentate inner molecular layer (IML) after 10-31 days indicative of MFS. Strong /"CD44"/ immunoreactivity appeared in the IML 3 days after pilocarpine, then declined over the next 4 weeks. Conversely, GAP-43 immunoreactivity was decreased in the IML at 3-10 days after pilocarpine-induced SE. After SE induced by repeated kainate injections, mice did not show any hilar cell loss or changes in /"CD44"/ or GAP-43 expression in the IML, and MFS was absent at 20-35 days. Thus, after SE in mice, early loss of GAP-43 and strong /"CD44"/ induction in the IML correlated with hilar cell loss and subsequent MFS. /"CD44"/ is one of the earliest proteins upregulated in the IML and coincides with early sprouting of mossy fibers, although its function is still unknown. We hypothesize that /"CD44"/ is involved in the response to axon /"terminal degeneration"/ and/or neuronal reorganization preceding MFS. | [
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} | Yes |
15191797 | Reciprocal changes of CD44 and GAP-43 expression in the dentate gyrus inner molecular layer after status epilepticus in mice. | Mossy fiber sprouting (MFS), a common feature of human temporal lobe epilepsy and many epilepsy animal models, contributes to hippocampal hyperexcitability. The molecular events responsible for MFS are not well understood, although the growth-associated protein GAP-43 has been implicated in rats. Here, we focus on the hyaluronan receptor CD44, which is involved in routing of retinal axons during development and is upregulated after injury in many tissues including brain. After pilocarpine-induced status epilepticus (SE) in mice most hilar neurons died and neuropeptide Y (NPY) immunoreactivity appeared in the dentate inner molecular layer (IML) after 10-31 days indicative of MFS. Strong CD44 immunoreactivity appeared in the IML 3 days after pilocarpine, then declined over the next 4 weeks. Conversely, GAP-43 immunoreactivity was decreased in the IML at 3-10 days after pilocarpine-induced SE. After SE induced by repeated kainate injections, mice did not show any hilar cell loss or changes in CD44 or GAP-43 expression in the IML, and MFS was absent at 20-35 days. Thus, after SE in mice, early loss of GAP-43 and strong CD44 induction in the IML correlated with hilar cell loss and subsequent MFS. CD44 is one of the earliest proteins upregulated in the IML and coincides with early sprouting of mossy fibers, although its function is still unknown. We hypothesize that CD44 is involved in the response to axon terminal degeneration and/or neuronal reorganization preceding MFS. | Reciprocal changes of CD44 and /"GAP-43"/ expression in the dentate gyrus inner molecular layer after status epilepticus in mice. | /"Mossy fiber sprouting"/ (/"MFS"/), a common feature of human temporal lobe epilepsy and many epilepsy animal models, contributes to hippocampal hyperexcitability. The molecular events responsible for /"MFS"/ are not well understood, although the growth-associated protein /"GAP-43"/ has been implicated in rats. Here, we focus on the hyaluronan receptor CD44, which is involved in routing of retinal axons during development and is upregulated after injury in many tissues including brain. After pilocarpine-induced status epilepticus (SE) in mice most hilar neurons died and neuropeptide Y (NPY) immunoreactivity appeared in the dentate inner molecular layer (IML) after 10-31 days indicative of /"MFS"/. Strong CD44 immunoreactivity appeared in the IML 3 days after pilocarpine, then declined over the next 4 weeks. Conversely, /"GAP-43"/ immunoreactivity was decreased in the IML at 3-10 days after pilocarpine-induced SE. After SE induced by repeated kainate injections, mice did not show any hilar cell loss or changes in CD44 or /"GAP-43"/ expression in the IML, and /"MFS"/ was absent at 20-35 days. Thus, after SE in mice, early loss of /"GAP-43"/ and strong CD44 induction in the IML correlated with hilar cell loss and subsequent /"MFS"/. CD44 is one of the earliest proteins upregulated in the IML and coincides with early sprouting of mossy fibers, although its function is still unknown. We hypothesize that CD44 is involved in the response to axon terminal degeneration and/or neuronal reorganization preceding /"MFS"/. | [
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} | No |
15201134 | TOLL-like receptor 10 genetic variation is associated with asthma in two independent samples. | TOLL-like receptor 10 (TLR10) is the most recently identified human homolog of the Drosophila TOLL protein. In humans, the TOLL-like receptors recognize pathogen-associated molecular patterns (PAMPs) as part of innate immune host defenses. Localized to chromosome 4p14, the specific ligands and functions of TLR10 are currently unknown, although it is expressed in lung and in B-lymphocytes. TLR10 is a potential asthma candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence asthma susceptibility. Resequencing in 47 subjects revealed a total of 78 single nucleotide polymorphisms (SNPS) (1 SNP per 106 bp) of which only 11 had been previously published. A significant association (p < or = 0.02) between two SNPs (c.+1031G>A, c.+2322A>G) and physician-diagnosed asthma was observed in a case control study (517 cases, 519 control subjects) of European American subjects nested within the Nurses' Health Study cohort. The association for these same two SNPs (p < or = 0.015) replicated in an independent family based cohort, where a measure of airway hyperresponsiveness (PC20) was also associated (p = 0.026 for c.+1031G>A). Consistent association in two independent samples and association with an intermediate phenotype provides strong support for TLR10 genetic variation contributing to asthma risk. | /"TOLL-like receptor 10"/ genetic variation is associated with /"asthma"/ in two independent samples. | /"TOLL-like receptor 10"/ (/"TLR10"/) is the most recently identified human homolog of the Drosophila TOLL protein. In humans, the TOLL-like receptors recognize pathogen-associated molecular patterns (PAMPs) as part of innate immune host defenses. Localized to chromosome 4p14, the specific ligands and functions of /"TLR10"/ are currently unknown, although it is expressed in lung and in B-lymphocytes. /"TLR10"/ is a potential /"asthma"/ candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence /"asthma"/ susceptibility. Resequencing in 47 subjects revealed a total of 78 single nucleotide polymorphisms (SNPS) (1 SNP per 106 bp) of which only 11 had been previously published. A significant association (p < or = 0.02) between two SNPs (c.+1031G>A, c.+2322A>G) and physician-diagnosed /"asthma"/ was observed in a case control study (517 cases, 519 control subjects) of European American subjects nested within the Nurses' Health Study cohort. The association for these same two SNPs (p < or = 0.015) replicated in an independent family based cohort, where a measure of airway hyperresponsiveness (PC20) was also associated (p = 0.026 for c.+1031G>A). Consistent association in two independent samples and association with an intermediate phenotype provides strong support for /"TLR10"/ genetic variation contributing to /"asthma"/ risk. | [
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15201134 | TOLL-like receptor 10 genetic variation is associated with asthma in two independent samples. | TOLL-like receptor 10 (TLR10) is the most recently identified human homolog of the Drosophila TOLL protein. In humans, the TOLL-like receptors recognize pathogen-associated molecular patterns (PAMPs) as part of innate immune host defenses. Localized to chromosome 4p14, the specific ligands and functions of TLR10 are currently unknown, although it is expressed in lung and in B-lymphocytes. TLR10 is a potential asthma candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence asthma susceptibility. Resequencing in 47 subjects revealed a total of 78 single nucleotide polymorphisms (SNPS) (1 SNP per 106 bp) of which only 11 had been previously published. A significant association (p < or = 0.02) between two SNPs (c.+1031G>A, c.+2322A>G) and physician-diagnosed asthma was observed in a case control study (517 cases, 519 control subjects) of European American subjects nested within the Nurses' Health Study cohort. The association for these same two SNPs (p < or = 0.015) replicated in an independent family based cohort, where a measure of airway hyperresponsiveness (PC20) was also associated (p = 0.026 for c.+1031G>A). Consistent association in two independent samples and association with an intermediate phenotype provides strong support for TLR10 genetic variation contributing to asthma risk. | TOLL-like receptor 10 genetic variation is associated with /"asthma"/ in two independent samples. | TOLL-like receptor 10 (TLR10) is the most recently identified human homolog of the Drosophila /"TOLL"/ protein. In humans, the /"TOLL"/-like receptors recognize pathogen-associated molecular patterns (PAMPs) as part of innate immune host defenses. Localized to chromosome 4p14, the specific ligands and functions of TLR10 are currently unknown, although it is expressed in lung and in B-lymphocytes. TLR10 is a potential /"asthma"/ candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence /"asthma"/ susceptibility. Resequencing in 47 subjects revealed a total of 78 single nucleotide polymorphisms (SNPS) (1 SNP per 106 bp) of which only 11 had been previously published. A significant association (p < or = 0.02) between two SNPs (c.+1031G>A, c.+2322A>G) and physician-diagnosed /"asthma"/ was observed in a case control study (517 cases, 519 control subjects) of European American subjects nested within the Nurses' Health Study cohort. The association for these same two SNPs (p < or = 0.015) replicated in an independent family based cohort, where a measure of airway hyperresponsiveness (PC20) was also associated (p = 0.026 for c.+1031G>A). Consistent association in two independent samples and association with an intermediate phenotype provides strong support for TLR10 genetic variation contributing to /"asthma"/ risk. | [
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15207432 | Common polymorphisms in methylenetetrahydrofolate reductase (MTHFR): relationships with plasma homocysteine concentrations and cognitive status in elderly northern italian subjects. | Hyperhomocysteinemia may be a risk factor for cognitive impairment. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine (Hcy) metabolism. Both the MTHFR 677C-->T and the 1298A-->C polymorphisms are associated with mild hyperhomocysteinemia, particularly in conditions of low folate status. The prevalence of these MTHFR polymorphisms and their relationships with plasma total Hcy (tHcy), serum folate and cognitive function was evaluated in 194 elderly Italian individuals: 122 healthy controls (73.8 +/- 7.1 years of age), 24 cognitively- impaired- not-demented individuals (78.6 +/- 9.3 years), and 48 subjects with Alzheimer dementia (AD = 26), vascular dementia (VD =22; 85.5 +/- 7.0 years). Twenty-one percent of all subjects were homozygous for 677C-->T and 7 % for 1298A-->C polymorphism. No significant relationship was found betweenMTHFR polymorphisms and age, cognitive status and type of dementia. Plasma tHcy did not differ significantly by MTHFR genotypes, but, subjects of all genotypes with low serum folate (<12 nmole/l) had higher plasma tHcy (p < 0.001), than subjects with high serum folate (>= 12 nmole/l). The study suggests that 677C-->T and 1298A-->C polymorphisms are common in the Northern Italian population, but do not significantly affect plasma tHcy levels of elderly individuals, even under conditions of low folate status. The lack of association of age and cognitive function with MTHFR genotypes argues against a negative selection for these polymorphisms. | Common polymorphisms in /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/): relationships with plasma homocysteine concentrations and cognitive status in elderly northern italian subjects. | /"Hyperhomocysteinemia"/ may be a risk factor for cognitive impairment. /"Methylenetetrahydrofolate reductase"/ (/"MTHFR"/) is a key enzyme in homocysteine (Hcy) metabolism. Both the /"MTHFR"/ 677C-->T and the 1298A-->C polymorphisms are associated with mild /"hyperhomocysteinemia"/, particularly in conditions of low folate status. The prevalence of these /"MTHFR"/ polymorphisms and their relationships with plasma total Hcy (tHcy), serum folate and cognitive function was evaluated in 194 elderly Italian individuals: 122 healthy controls (73.8 +/- 7.1 years of age), 24 cognitively- impaired- not-demented individuals (78.6 +/- 9.3 years), and 48 subjects with Alzheimer dementia (AD = 26), vascular dementia (VD =22; 85.5 +/- 7.0 years). Twenty-one percent of all subjects were homozygous for 677C-->T and 7 % for 1298A-->C polymorphism. No significant relationship was found betweenMTHFR polymorphisms and age, cognitive status and type of dementia. Plasma tHcy did not differ significantly by /"MTHFR"/ genotypes, but, subjects of all genotypes with low serum folate (<12 nmole/l) had higher plasma tHcy (p < 0.001), than subjects with high serum folate (>= 12 nmole/l). The study suggests that 677C-->T and 1298A-->C polymorphisms are common in the Northern Italian population, but do not significantly affect plasma tHcy levels of elderly individuals, even under conditions of low folate status. The lack of association of age and cognitive function with /"MTHFR"/ genotypes argues against a negative selection for these polymorphisms. | [
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15207432 | Common polymorphisms in methylenetetrahydrofolate reductase (MTHFR): relationships with plasma homocysteine concentrations and cognitive status in elderly northern italian subjects. | Hyperhomocysteinemia may be a risk factor for cognitive impairment. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine (Hcy) metabolism. Both the MTHFR 677C-->T and the 1298A-->C polymorphisms are associated with mild hyperhomocysteinemia, particularly in conditions of low folate status. The prevalence of these MTHFR polymorphisms and their relationships with plasma total Hcy (tHcy), serum folate and cognitive function was evaluated in 194 elderly Italian individuals: 122 healthy controls (73.8 +/- 7.1 years of age), 24 cognitively- impaired- not-demented individuals (78.6 +/- 9.3 years), and 48 subjects with Alzheimer dementia (AD = 26), vascular dementia (VD =22; 85.5 +/- 7.0 years). Twenty-one percent of all subjects were homozygous for 677C-->T and 7 % for 1298A-->C polymorphism. No significant relationship was found betweenMTHFR polymorphisms and age, cognitive status and type of dementia. Plasma tHcy did not differ significantly by MTHFR genotypes, but, subjects of all genotypes with low serum folate (<12 nmole/l) had higher plasma tHcy (p < 0.001), than subjects with high serum folate (>= 12 nmole/l). The study suggests that 677C-->T and 1298A-->C polymorphisms are common in the Northern Italian population, but do not significantly affect plasma tHcy levels of elderly individuals, even under conditions of low folate status. The lack of association of age and cognitive function with MTHFR genotypes argues against a negative selection for these polymorphisms. | Common polymorphisms in /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/): relationships with plasma homocysteine concentrations and cognitive status in elderly northern italian subjects. | Hyperhomocysteinemia may be a risk factor for cognitive impairment. /"Methylenetetrahydrofolate reductase"/ (/"MTHFR"/) is a key enzyme in homocysteine (Hcy) metabolism. Both the /"MTHFR"/ 677C-->T and the 1298A-->C polymorphisms are associated with mild hyperhomocysteinemia, particularly in conditions of low folate status. The prevalence of these /"MTHFR"/ polymorphisms and their relationships with plasma total Hcy (tHcy), serum folate and cognitive function was evaluated in 194 elderly Italian individuals: 122 healthy controls (73.8 +/- 7.1 years of age), 24 cognitively- impaired- not-demented individuals (78.6 +/- 9.3 years), and 48 subjects with Alzheimer dementia (AD = 26), /"vascular dementia"/ (VD =22; 85.5 +/- 7.0 years). Twenty-one percent of all subjects were homozygous for 677C-->T and 7 % for 1298A-->C polymorphism. No significant relationship was found betweenMTHFR polymorphisms and age, cognitive status and type of dementia. Plasma tHcy did not differ significantly by /"MTHFR"/ genotypes, but, subjects of all genotypes with low serum folate (<12 nmole/l) had higher plasma tHcy (p < 0.001), than subjects with high serum folate (>= 12 nmole/l). The study suggests that 677C-->T and 1298A-->C polymorphisms are common in the Northern Italian population, but do not significantly affect plasma tHcy levels of elderly individuals, even under conditions of low folate status. The lack of association of age and cognitive function with /"MTHFR"/ genotypes argues against a negative selection for these polymorphisms. | [
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15228651 | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the HLA-A, -B, -DRB1 molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of HLA-A, -B and -DRB1 between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting /"acute graft versus host disease"/ (/"aGVHD"/) after unrelated cord blood transplantation (UCBT), the /"HLA-A, -B, -DRB1"/ molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of /"HLA-A, -B and -DRB1"/ between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop /"aGVHD"/; the second group developed /"aGVHD"/ graded I-II and the third group developed /"aGVHD"/ graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop /"aGVHD"/ (32%); 13 patients in the second group developed grade I-II of /"aGVHD"/ (52%) and 4 patients in the third group developed /"aGVHD III-IV"/ (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe /"aGVHD"/ after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe /"aGVHD"/ for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [
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15228651 | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the HLA-A, -B, -DRB1 molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of HLA-A, -B and -DRB1 between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting /"acute graft versus host disease"/ (/"aGVHD"/) after unrelated cord blood transplantation (UCBT), the /"HLA-A, -B, -DRB1"/ molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of /"HLA-A, -B and -DRB1"/ between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop /"aGVHD"/; the second group developed /"aGVHD"/ graded I-II and the third group developed /"aGVHD"/ graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop /"aGVHD"/ (32%); 13 patients in the second group developed grade I-II of /"aGVHD"/ (52%) and 4 patients in the third group developed /"aGVHD III-IV"/ (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe /"aGVHD"/ after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe /"aGVHD"/ for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [
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15228651 | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the HLA-A, -B, -DRB1 molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of HLA-A, -B and -DRB1 between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting /"acute graft versus host disease"/ (/"aGVHD"/) after unrelated cord blood transplantation (UCBT), the /"HLA-A, -B, -DRB1"/ molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of /"HLA-A, -B and -DRB1"/ between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop /"aGVHD"/; the second group developed /"aGVHD"/ graded I-II and the third group developed /"aGVHD"/ graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop /"aGVHD"/ (32%); 13 patients in the second group developed grade I-II of /"aGVHD"/ (52%) and 4 patients in the third group developed /"aGVHD III-IV"/ (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe /"aGVHD"/ after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe /"aGVHD"/ for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [
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15228651 | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the HLA-A, -B, -DRB1 molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of HLA-A, -B and -DRB1 between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the /"HLA-A, -B, -DRB1"/ molecular three-dimensional structures in 25 patients with /"blood disorder"/ who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of /"HLA-A, -B and -DRB1"/ between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [
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15228651 | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the HLA-A, -B, -DRB1 molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of HLA-A, -B and -DRB1 between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the /"HLA-A, -B, -DRB1"/ molecular three-dimensional structures in 25 patients with /"blood disorder"/ who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of /"HLA-A, -B and -DRB1"/ between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [
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15228651 | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the HLA-A, -B, -DRB1 molecular three-dimensional structures in 25 patients with blood disorder who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of HLA-A, -B and -DRB1 between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [Prediction of acute GVHD after umbilical cord blood transplantation by HLA three-dimensional structure matching]. | To explore a method of predicting acute graft versus host disease (aGVHD) after unrelated cord blood transplantation (UCBT), the /"HLA-A, -B, -DRB1"/ molecular three-dimensional structures in 25 patients with /"blood disorder"/ who underwent UCBT and their donors were modeled by using molecular modeling technique. First, full amino acid sequences of each HLA antigen from HLA data banks were loaded down, and then amino acid sequence of extracellular antigen binding region was chosen. Third step, SPDBV software of SWISS-MODEL server was used to modeling the three-dimensional structures of each different allele of /"HLA-A, -B and -DRB1"/ between patients and donors and the parameter "root mean square deviation" (RMSD) was used to indicate the structure differences. Last, RMSD of each different HLA allele of each donor-patient pair were added together to get total RMSD. The 25 patients were divided into 3 groups: the first group did not develop aGVHD; the second group developed aGVHD graded I-II and the third group developed aGVHD graded III-IV. The results showed that in the 25 patients divided into three groups, 8 patients in the first group did not develop aGVHD (32%); 13 patients in the second group developed grade I-II of aGVHD (52%) and 4 patients in the third group developed aGVHD III-IV (16%). The total RMSDs of each group were 0.24 +/- 0.15, 0.25 +/- 0.14 and 0.47 +/- 0.22 respectively. The total RMSD of the third group was significantly higher than that of the other two groups. In conclusion, utilization of modeling HLA molecular three-dimension can predict the severe aGVHD after UCBT quickly, simply and accurately. It provides scientific basis in choosing a optimal cord blood donor to avoid severe aGVHD for physicians and the cord blood banks. And it is instructive too to direct the application of immunosuppressive agents after transplantation in clinic. | [
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"entity_type": "Gene",
"text_name": "HLA-A, -B and -DRB1"
},
{
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"end_idx": "260",
"entity_id": "3123",
"entity_type": "Gene",
"text_name": "HLA-A, -B, -DRB1"
},
{
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"end_idx": "745",
"entity_id": "3123",
"entity_type": "Gene",
"text_name": "HLA-A, -B and -DRB1"
}
] | {
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"text_name": "HLA-A, -B, -DRB1"
} | {
"begin_idx": "320",
"end_idx": "334",
"entity_id": "D025861",
"entity_type": "Disease",
"text_name": "blood disorder"
} | No |
15253766 | Spectrum and frequencies of mutations in the GJB2 (Cx26) gene among 156 Czech patients with pre-lingual deafness. | Mutations in the gene gap junction beta 2 (GJB2), the gene for the connexin 26, are the most common cause of pre-lingual deafness worldwide. The mutation 35delG within GJB2 is prevalent in Europe. To date, there are no data about GJB2 mutation spectrum and frequencies from the Czech population. We investigated and report here the spectrum and frequencies of mutations in the GJB2 gene among 156 unrelated, congenital deafness Czech patients. Allele-specific polymerase chain reaction, together with fluorescent fragment analysis, were used for the detection of the 35delG mutation. The entire coding region of the GJB2 was directly sequenced in all patients who were not homozygous for the 35delG. No pathogenic mutation was detected in 51.9% of patients. At least one pathogenic mutation was found in 48.1% of patients, and both pathogenic mutations were detected in 37.8% of patients. Single mutations in a heterozygous state were detected in 10.3% of patients. The mutation 35delG accounts for 82.8% of detected disease mutations, Trp24stop accounts for 9.7% of pathogenic alleles and was found in patients with gypsy heritage. Mutation 313del14 accounts for 3.7% of pathogenic alleles. The frequency of 35delG heterozygotes in the Czech Republic is 1 : 29.6. Testing for only the three most common mutations would detect over 96% of all pathogenic alleles in the Czech Republic. | Spectrum and frequencies of mutations in the /"GJB2"/ (/"Cx26"/) gene among 156 Czech patients with /"pre-lingual deafness"/. | Mutations in the gene /"gap junction beta 2"/ (/"GJB2"/), the gene for the /"connexin 26"/, are the most common cause of /"pre-lingual deafness"/ worldwide. The mutation 35delG within /"GJB2"/ is prevalent in Europe. To date, there are no data about /"GJB2"/ mutation spectrum and frequencies from the Czech population. We investigated and report here the spectrum and frequencies of mutations in the /"GJB2"/ gene among 156 unrelated, /"congenital deafness"/ Czech patients. Allele-specific polymerase chain reaction, together with fluorescent fragment analysis, were used for the detection of the 35delG mutation. The entire coding region of the /"GJB2"/ was directly sequenced in all patients who were not homozygous for the 35delG. No pathogenic mutation was detected in 51.9% of patients. At least one pathogenic mutation was found in 48.1% of patients, and both pathogenic mutations were detected in 37.8% of patients. Single mutations in a heterozygous state were detected in 10.3% of patients. The mutation 35delG accounts for 82.8% of detected disease mutations, Trp24stop accounts for 9.7% of pathogenic alleles and was found in patients with gypsy heritage. Mutation 313del14 accounts for 3.7% of pathogenic alleles. The frequency of 35delG heterozygotes in the Czech Republic is 1 : 29.6. Testing for only the three most common mutations would detect over 96% of all pathogenic alleles in the Czech Republic. | [
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}
] | {
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"entity_type": "Gene",
"text_name": "gap junction beta 2"
} | {
"begin_idx": "92",
"end_idx": "112",
"entity_id": "D003638",
"entity_type": "Disease",
"text_name": "pre-lingual deafness"
} | Yes |
15255109 | Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador. | PURPOSE: To determine the role of cytochrome P450IBI (CYP1B1) mutations in causing primary congenital glaucoma (PCG) in a cohort of Native Americans from Quito, Ecuador. MATERIALS AND METHODS: Seventeen patients with PCG from 15 Native American families were recruited from the Ophthalmology Clinic at Hospital Metropolitano, Quito, Ecuador. Experienced ophthalmologists examined all affected study subjects. Purified DNA was prepared from peripheral blood samples and CYP1B1 coding exons (exons 2 and 3) were amplified and sequenced. Southern blot was performed only on those affected patients who showed no mutations in the CYP1B1 coding exons. RESULTS: The molecular basis of PCG in two families was determined: two novel mutations (a deletion and a point mutation) and one novel polymorphism in CYP1B1 were identified in addition to a previously described single amino acid substitution. Southern blot analyses on whole genomic DNA from affected individuals in whom no mutations were identified by the direct PCR/sequencing approach did not detect any large rearrangements or mutations outside the coding region. CONCLUSION: These findings suggest that mutations in CYPIBI are not a major cause of PCG in this population and that at least one additional locus for this condition is responsible for most cases. Further, the PCG phenotype did not correlate readily with the molecular basis of the disorder, suggesting that careful clinical analysis of the phenotype cannot predict the molecular basis of the disease with accuracy. | Cytochrome P4501B1 mutations cause only part of primary /"congenital glaucoma"/ in Ecuador. | PURPOSE: To determine the role of cytochrome P450IBI (/"CYP1B1"/) mutations in causing primary /"congenital glaucoma"/ (PCG) in a cohort of Native Americans from Quito, Ecuador. MATERIALS AND METHODS: Seventeen patients with PCG from 15 Native American families were recruited from the Ophthalmology Clinic at Hospital Metropolitano, Quito, Ecuador. Experienced ophthalmologists examined all affected study subjects. Purified DNA was prepared from peripheral blood samples and /"CYP1B1"/ coding exons (exons 2 and 3) were amplified and sequenced. Southern blot was performed only on those affected patients who showed no mutations in the /"CYP1B1"/ coding exons. RESULTS: The molecular basis of PCG in two families was determined: two novel mutations (a deletion and a point mutation) and one novel polymorphism in /"CYP1B1"/ were identified in addition to a previously described single amino acid substitution. Southern blot analyses on whole genomic DNA from affected individuals in whom no mutations were identified by the direct PCR/sequencing approach did not detect any large rearrangements or mutations outside the coding region. CONCLUSION: These findings suggest that mutations in CYPIBI are not a major cause of PCG in this population and that at least one additional locus for this condition is responsible for most cases. Further, the PCG phenotype did not correlate readily with the molecular basis of the disorder, suggesting that careful clinical analysis of the phenotype cannot predict the molecular basis of the disease with accuracy. | [
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} | {
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"entity_id": "C565547",
"entity_type": "Disease",
"text_name": "congenital glaucoma"
} | Yes |
15256764 | Mutations in Japanese subjects with primary hyperlipidemia--results from the Research Committee of the Ministry of Health and Welfare of Japan since 1996--. | Primary hyperlipidemia is caused by various molecular defects in lipid metabolism. The Research Committee on Primary Hyperlipidemia organized by the Ministry of Health and Welfare of Japan (present: the Ministry of Health, Labour and Welfare) has investigated reported mutations in Japanese patients with primary hyperlipidemia and related disorders (including hypolipidemia), and has created a database based on the questionnaire sent to the members of council board of the Japan Atherosclerosis Society. Mutations in the following genes were investigated: low density lipoprotein receptor, lecithin: cholesteryl acyltransferase, lipoprotein lipase (LPL), hepatic lipase, apolipoproteins A-I, A-II, A-IV, B, C-II, C-III and E, microsomal triglyceride transfer protein, and cholesterol ester transfer protein (CETP). Until 1998, 922 patients with primary hyperlipidemia and related disorders has been registered with the Research Committee, and 190 mutations in 15 genes had been reported, showing a marked variation in Japanese patients with primary hyperlipidemia and related disorders. So-called "common mutations" have been described in Japanese patients with familial hypercholesterolemia, LPL deficiency and CETP deficiency. The genetic defect of familial combined hyperlipidemia (FCHL) is still unknown although FCHL is speculated to be the most prevalent genetic hyperlipidemia, and further investigations should be performed to elucidate the molecular mechanisms of FCHL | Mutations in Japanese subjects with primary hyperlipidemia--results from the Research Committee of the Ministry of Health and Welfare of Japan since 1996--. | Primary hyperlipidemia is caused by various molecular defects in lipid metabolism. The Research Committee on Primary Hyperlipidemia organized by the Ministry of Health and Welfare of Japan (present: the Ministry of Health, Labour and Welfare) has investigated reported mutations in Japanese patients with primary hyperlipidemia and related disorders (including hypolipidemia), and has created a database based on the questionnaire sent to the members of council board of the Japan Atherosclerosis Society. Mutations in the following genes were investigated: low density lipoprotein receptor, lecithin: cholesteryl acyltransferase, /"lipoprotein lipase"/ (/"LPL"/), hepatic lipase, apolipoproteins A-I, A-II, A-IV, B, C-II, C-III and E, microsomal triglyceride transfer protein, and cholesterol ester transfer protein (CETP). Until 1998, 922 patients with primary hyperlipidemia and related disorders has been registered with the Research Committee, and 190 mutations in 15 genes had been reported, showing a marked variation in Japanese patients with primary hyperlipidemia and related disorders. So-called "common mutations" have been described in Japanese patients with familial hypercholesterolemia, /"LPL deficiency"/ and CETP deficiency. The genetic defect of familial combined hyperlipidemia (FCHL) is still unknown although FCHL is speculated to be the most prevalent genetic hyperlipidemia, and further investigations should be performed to elucidate the molecular mechanisms of FCHL | [
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},
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},
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},
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"text_name": "Atherosclerosis"
},
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},
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}
] | {
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} | {
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"entity_id": "D008072",
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"text_name": "LPL deficiency"
} | Yes |
15256764 | Mutations in Japanese subjects with primary hyperlipidemia--results from the Research Committee of the Ministry of Health and Welfare of Japan since 1996--. | Primary hyperlipidemia is caused by various molecular defects in lipid metabolism. The Research Committee on Primary Hyperlipidemia organized by the Ministry of Health and Welfare of Japan (present: the Ministry of Health, Labour and Welfare) has investigated reported mutations in Japanese patients with primary hyperlipidemia and related disorders (including hypolipidemia), and has created a database based on the questionnaire sent to the members of council board of the Japan Atherosclerosis Society. Mutations in the following genes were investigated: low density lipoprotein receptor, lecithin: cholesteryl acyltransferase, lipoprotein lipase (LPL), hepatic lipase, apolipoproteins A-I, A-II, A-IV, B, C-II, C-III and E, microsomal triglyceride transfer protein, and cholesterol ester transfer protein (CETP). Until 1998, 922 patients with primary hyperlipidemia and related disorders has been registered with the Research Committee, and 190 mutations in 15 genes had been reported, showing a marked variation in Japanese patients with primary hyperlipidemia and related disorders. So-called "common mutations" have been described in Japanese patients with familial hypercholesterolemia, LPL deficiency and CETP deficiency. The genetic defect of familial combined hyperlipidemia (FCHL) is still unknown although FCHL is speculated to be the most prevalent genetic hyperlipidemia, and further investigations should be performed to elucidate the molecular mechanisms of FCHL | Mutations in Japanese subjects with primary hyperlipidemia--results from the Research Committee of the Ministry of Health and Welfare of Japan since 1996--. | Primary hyperlipidemia is caused by various molecular defects in lipid metabolism. The Research Committee on Primary Hyperlipidemia organized by the Ministry of Health and Welfare of Japan (present: the Ministry of Health, Labour and Welfare) has investigated reported mutations in Japanese patients with primary hyperlipidemia and related disorders (including hypolipidemia), and has created a database based on the questionnaire sent to the members of council board of the Japan Atherosclerosis Society. Mutations in the following genes were investigated: /"low density lipoprotein receptor"/, lecithin: cholesteryl acyltransferase, lipoprotein lipase (LPL), hepatic lipase, apolipoproteins A-I, A-II, A-IV, B, C-II, C-III and E, microsomal triglyceride transfer protein, and cholesterol ester transfer protein (CETP). Until 1998, 922 patients with primary hyperlipidemia and related disorders has been registered with the Research Committee, and 190 mutations in 15 genes had been reported, showing a marked variation in Japanese patients with primary hyperlipidemia and related disorders. So-called "common mutations" have been described in Japanese patients with familial hypercholesterolemia, LPL deficiency and CETP deficiency. The genetic defect of /"familial combined hyperlipidemia"/ (/"FCHL"/) is still unknown although /"FCHL"/ is speculated to be the most prevalent genetic hyperlipidemia, and further investigations should be performed to elucidate the molecular mechanisms of /"FCHL"/ | [
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},
{
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},
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},
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},
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"text_name": "lipoprotein lipase"
},
{
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"entity_id": "4023",
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"text_name": "LPL"
}
] | {
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"entity_id": "3949",
"entity_type": "Gene",
"text_name": "low density lipoprotein receptor"
} | {
"begin_idx": "1476",
"end_idx": "1480",
"entity_id": "D006950",
"entity_type": "Disease",
"text_name": "FCHL"
} | No |
15257748 | Genetic variations in the matrix metalloproteinase-1 promoter and risk of susceptibility and/or severity of chronic periodontitis in the Czech population. | OBJECTIVES: Matrix metalloproteinase-1 (MMP-1) is a potent enzyme degrading extracellular matrix that was implicated in the pathogenesis of chronic periodontitis. Therefore, the aim of our study was to examine the association between three promoter polymorphisms of the MMP-1 gene and chronic periodontitis susceptibility and/or severity in a Czech population. MATERIALS AND METHODS: A total of 329 Caucasian subjects were enrolled in this study. They were 133 patients with mild to severe chronic periodontitis and 196 unrelated control subjects. MMP-1 promoter polymorphisms (-1607 1G/2G, -519A/G, and -422A/T) were genotyped using standard polymerase chain reaction-restriction fragment length product methods. RESULTS: Genotype analysis of the three single nucleotide polymorphisms across 27 different combinations showed significant association with chronic periodontitis (p<0.05). Analyses of individual polymorphisms showed no differences in distribution of the -519A/G and -422A/T variants between periodontitis and control groups. However, a trend to increased frequency of the -1607 1G allele was observed in patients with chronic periodontitis compared with the controls (p=0.054). When the groups were further stratified by smoking status, the 1G allele was associated with chronic periodontitis among non-smokers but not among smokers (p=0.033). On the contrary, the distribution of genotype frequencies of the MMP-1 -422A/T polymorphism was different between the patient and control smokers with respect to heterozygotes (73.91% versus 50.91%; p=0.017). CONCLUSIONS: Our results demonstrate that the polymorphisms in the MMP-1 promoter may have only a small effect on the etiopathogenesis of chronic periodontitis. | Genetic variations in the /"matrix metalloproteinase-1"/ promoter and risk of susceptibility and/or severity of chronic periodontitis in the Czech population. | OBJECTIVES: /"Matrix metalloproteinase-1"/ (/"MMP-1"/) is a potent enzyme degrading extracellular matrix that was implicated in the pathogenesis of chronic periodontitis. Therefore, the aim of our study was to examine the association between three promoter polymorphisms of the /"MMP-1"/ gene and chronic periodontitis susceptibility and/or severity in a Czech population. MATERIALS AND METHODS: A total of 329 Caucasian subjects were enrolled in this study. They were 133 patients with mild to severe chronic periodontitis and 196 unrelated control subjects. /"MMP-1"/ promoter polymorphisms (-1607 1G/2G, -519A/G, and -422A/T) were genotyped using standard polymerase chain reaction-restriction fragment length product methods. RESULTS: Genotype analysis of the three single nucleotide polymorphisms across 27 different combinations showed significant association with chronic periodontitis (p<0.05). Analyses of individual polymorphisms showed no differences in distribution of the -519A/G and -422A/T variants between /"periodontitis"/ and control groups. However, a trend to increased frequency of the -1607 1G allele was observed in patients with chronic periodontitis compared with the controls (p=0.054). When the groups were further stratified by smoking status, the 1G allele was associated with chronic periodontitis among non-smokers but not among smokers (p=0.033). On the contrary, the distribution of genotype frequencies of the /"MMP-1"/ -422A/T polymorphism was different between the patient and control smokers with respect to heterozygotes (73.91% versus 50.91%; p=0.017). CONCLUSIONS: Our results demonstrate that the polymorphisms in the /"MMP-1"/ promoter may have only a small effect on the etiopathogenesis of chronic periodontitis. | [
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"text_name": "periodontitis"
} | Yes |
15257748 | Genetic variations in the matrix metalloproteinase-1 promoter and risk of susceptibility and/or severity of chronic periodontitis in the Czech population. | OBJECTIVES: Matrix metalloproteinase-1 (MMP-1) is a potent enzyme degrading extracellular matrix that was implicated in the pathogenesis of chronic periodontitis. Therefore, the aim of our study was to examine the association between three promoter polymorphisms of the MMP-1 gene and chronic periodontitis susceptibility and/or severity in a Czech population. MATERIALS AND METHODS: A total of 329 Caucasian subjects were enrolled in this study. They were 133 patients with mild to severe chronic periodontitis and 196 unrelated control subjects. MMP-1 promoter polymorphisms (-1607 1G/2G, -519A/G, and -422A/T) were genotyped using standard polymerase chain reaction-restriction fragment length product methods. RESULTS: Genotype analysis of the three single nucleotide polymorphisms across 27 different combinations showed significant association with chronic periodontitis (p<0.05). Analyses of individual polymorphisms showed no differences in distribution of the -519A/G and -422A/T variants between periodontitis and control groups. However, a trend to increased frequency of the -1607 1G allele was observed in patients with chronic periodontitis compared with the controls (p=0.054). When the groups were further stratified by smoking status, the 1G allele was associated with chronic periodontitis among non-smokers but not among smokers (p=0.033). On the contrary, the distribution of genotype frequencies of the MMP-1 -422A/T polymorphism was different between the patient and control smokers with respect to heterozygotes (73.91% versus 50.91%; p=0.017). CONCLUSIONS: Our results demonstrate that the polymorphisms in the MMP-1 promoter may have only a small effect on the etiopathogenesis of chronic periodontitis. | Genetic variations in the /"matrix metalloproteinase-1"/ promoter and risk of susceptibility and/or severity of /"chronic periodontitis"/ in the Czech population. | OBJECTIVES: /"Matrix metalloproteinase-1"/ (/"MMP-1"/) is a potent enzyme degrading extracellular matrix that was implicated in the pathogenesis of /"chronic periodontitis"/. Therefore, the aim of our study was to examine the association between three promoter polymorphisms of the /"MMP-1"/ gene and /"chronic periodontitis"/ susceptibility and/or severity in a Czech population. MATERIALS AND METHODS: A total of 329 Caucasian subjects were enrolled in this study. They were 133 patients with mild to severe /"chronic periodontitis"/ and 196 unrelated control subjects. /"MMP-1"/ promoter polymorphisms (-1607 1G/2G, -519A/G, and -422A/T) were genotyped using standard polymerase chain reaction-restriction fragment length product methods. RESULTS: Genotype analysis of the three single nucleotide polymorphisms across 27 different combinations showed significant association with /"chronic periodontitis"/ (p<0.05). Analyses of individual polymorphisms showed no differences in distribution of the -519A/G and -422A/T variants between periodontitis and control groups. However, a trend to increased frequency of the -1607 1G allele was observed in patients with /"chronic periodontitis"/ compared with the controls (p=0.054). When the groups were further stratified by smoking status, the 1G allele was associated with /"chronic periodontitis"/ among non-smokers but not among smokers (p=0.033). On the contrary, the distribution of genotype frequencies of the /"MMP-1"/ -422A/T polymorphism was different between the patient and control smokers with respect to heterozygotes (73.91% versus 50.91%; p=0.017). CONCLUSIONS: Our results demonstrate that the polymorphisms in the /"MMP-1"/ promoter may have only a small effect on the etiopathogenesis of /"chronic periodontitis"/. | [
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"text_name": "chronic periodontitis"
} | No |
15258326 | GSTT1 gene deletion is associated with lung cancer in Mexican patients. | Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking. We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer. | /"GSTT1"/ gene deletion is associated with /"lung cancer"/ in Mexican patients. | Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the /"GSTT1"/ gene (null genotype) may play a role in the induction of /"lung cancer"/ by smoking. We studied the distribution of /"GSTT1"/ gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 /"lung cancer"/ patients. Comparisons between groups showed that there was an /"increased lung cancer"/ risk for individuals with the /"GSTT1"/ null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of /"lung cancer"/ patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing /"lung cancer"/. | [
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"text_name": "increased lung cancer"
} | Yes |
15258326 | GSTT1 gene deletion is associated with lung cancer in Mexican patients. | Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking. We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer. | /"GSTT1"/ gene deletion is associated with lung cancer in Mexican patients. | Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, /"deficiency in GST activity"/ due to homozygous deletion of the /"GSTT1"/ gene (null genotype) may play a role in the induction of lung cancer by smoking. We studied the distribution of /"GSTT1"/ gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the /"GSTT1"/ null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer. | [
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15266614 | Does bilirubin protect against hemochromatosis gene (HFE) related mortality? | Serum bilirubin is an important antioxidant that is found at increased levels in hereditary hemochromatosis patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by iron overload in carriers of mutations in the hereditary hemochromatosis gene (HFE). We studied the relation between serum total bilirubin, serum iron levels, the HFE C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population-based follow-up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), transferrin saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the HFE mutations had higher levels of bilirubin compared to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by iron overload. This may explain in part the reduced penetrance of the HFE mutations. | Does bilirubin protect against /"hemochromatosis"/ gene (/"HFE"/) related mortality? | Serum bilirubin is an important antioxidant that is found at increased levels in hereditary /"hemochromatosis"/ patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by /"iron overload"/ in carriers of mutations in the hereditary /"hemochromatosis"/ gene (/"HFE"/). We studied the relation between serum total bilirubin, serum iron levels, the /"HFE"/ C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population-based follow-up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), transferrin saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the /"HFE"/ mutations had higher levels of bilirubin compared to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by /"iron overload"/. This may explain in part the reduced penetrance of the /"HFE"/ mutations. | [
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15266614 | Does bilirubin protect against hemochromatosis gene (HFE) related mortality? | Serum bilirubin is an important antioxidant that is found at increased levels in hereditary hemochromatosis patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by iron overload in carriers of mutations in the hereditary hemochromatosis gene (HFE). We studied the relation between serum total bilirubin, serum iron levels, the HFE C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population-based follow-up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), transferrin saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the HFE mutations had higher levels of bilirubin compared to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by iron overload. This may explain in part the reduced penetrance of the HFE mutations. | Does bilirubin protect against /"hemochromatosis"/is"/ gene (/"HFE"/) related mortality? | Serum bilirubin is an important antioxidant that is found at increased levels in /"hereditary hemochromatosis"/is"/ patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by iron overload in carriers of mutations in the /"hereditary hemochromatosis"/is"/ gene (/"HFE"/). We studied the relation between serum total bilirubin, serum iron levels, the /"HFE"/ C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population-based follow-up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), transferrin saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the /"HFE"/ mutations had higher levels of bilirubin compared to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by iron overload. This may explain in part the reduced penetrance of the /"HFE"/ mutations. | [
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15266614 | Does bilirubin protect against hemochromatosis gene (HFE) related mortality? | Serum bilirubin is an important antioxidant that is found at increased levels in hereditary hemochromatosis patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by iron overload in carriers of mutations in the hereditary hemochromatosis gene (HFE). We studied the relation between serum total bilirubin, serum iron levels, the HFE C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population-based follow-up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), transferrin saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the HFE mutations had higher levels of bilirubin compared to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by iron overload. This may explain in part the reduced penetrance of the HFE mutations. | Does bilirubin protect against /"hemochromatosis"/ gene (HFE) related mortality? | Serum bilirubin is an important antioxidant that is found at increased levels in /"hereditary hemochromatosis"/ patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by iron overload in carriers of mutations in the /"hereditary hemochromatosis"/ gene (HFE). We studied the relation between serum total bilirubin, serum iron levels, the HFE C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population-based follow-up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), /"transferrin"/ saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the HFE mutations had higher levels of bilirubin compared to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by iron overload. This may explain in part the reduced penetrance of the HFE mutations. | [
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15266614 | Does bilirubin protect against hemochromatosis gene (HFE) related mortality? | Serum bilirubin is an important antioxidant that is found at increased levels in hereditary hemochromatosis patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by iron overload in carriers of mutations in the hereditary hemochromatosis gene (HFE). We studied the relation between serum total bilirubin, serum iron levels, the HFE C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population-based follow-up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), transferrin saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the HFE mutations had higher levels of bilirubin compared to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by iron overload. This may explain in part the reduced penetrance of the HFE mutations. | Does bilirubin protect against hemochromatosis gene (HFE) related mortality? | Serum bilirubin is an important antioxidant that is found at increased levels in hereditary hemochromatosis patients. We hypothesized that increased levels of serum bilirubin may play a protective role against oxidative stress induced by /"iron overload"/ in carriers of mutations in the hereditary hemochromatosis gene (HFE). We studied the relation between serum total bilirubin, serum iron levels, the HFE C282Y and H63D mutations, and mortality. The study was conducted in 2,332 randomly selected subjects from the Rotterdam Study, a population-based follow-up study of people aged 55 years or over. Serum bilirubin levels were significantly correlated with serum iron (Pearson's correlation coefficient (r) = 0.4, P < 0.001), /"transferrin"/ saturation (r = 0.4, P < 0.001), and serum ferritin (r = 0.2, P < 0.05). Carriers of the HFE mutations had higher levels of bilirubin compared to wild-type homozygotes. The relation was the strongest in H63D heterozygotes or homozygotes and C282Y heterozygotes. High levels of serum bilirubin were associated with a 2.8 (95% CI 0.9-8.8) fold reduction in mortality in H63D homozygotes and a 2.2 (1.0-4.7) fold reduction in mortality in C282Y heterozygotes. Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by /"iron overload"/. This may explain in part the reduced penetrance of the HFE mutations. | [
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15274044 | Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity. | The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. | Variants of the orexin2/hcrt2 receptor gene identified in patients with /"excessive daytime sleepiness"/ and patients with Tourette's syndrome comorbidity. | The orexin-2/hypocretin-2 (/"OX2R"/) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the /"OX2R"/ gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of /"sleep disorders"/. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in /"idiopathic sleep disorder"/ patients diagnosed with /"excessive daytime sleepiness"/ (/"EDS"/) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two /"EDS"/ patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by /"EDS"/. | [
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15274044 | Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity. | The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. | Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with /"Tourette's syndrome"/ comorbidity. | The orexin-2/hypocretin-2 (/"OX2R"/) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the /"OX2R"/ gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One /"Tourette's syndrome"/ patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. | [
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15274044 | Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity. | The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. | Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity. | The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine /"narcolepsy"/ and disruption of the /"prepro-orexin"//hypocretin ligand gene results in both an animal model of /"narcolepsy"/ and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the /"prepro-orexin"//hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), /"narcolepsy"/ (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. | [
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15274044 | Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity. | The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. | Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity. | The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine /"narcolepsy"/ and disruption of the /"prepro-orexin"//hypocretin ligand gene results in both an animal model of /"narcolepsy"/ and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the /"prepro-orexin"//hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), /"narcolepsy"/ (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS. | [
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15279649 | The 3020insC mutation of the NOD2/CARD15 gene in patients with periodontal disease. | The 3020insC mutation of the NOD2/CARD15 gene leads to impaired activation of nuclear factor-kappa B (NF-kappaB) in vitro. As the destruction of periodontal tissue is mediated via activation of NF-kappaB, with subsequent transcription of proinflammatory cytokines, the c-insertion mutation of the NOD2/CARD15 gene might contribute to the proposed genetic background of periodontitis. The present study analysed the frequency of this mutation in 80 patients with chronic periodontal disease and 122 healthy controls. The 3020insC mutation was identified by employing the polymerase chain reaction followed by restriction fragment length polymorphism analysis. The prevalence of the 3020insC mutation of the NOD2/CARD15 protein in patients with periodontitis was 1.9% (three of 160) and that for the control group was 2.0% (five of 244) (P = 0.942). Hence, unlike in Crohn's disease, the 3020insC mutation of the NOD2/CARD15 gene does not seem to influence the pathophysiology of periodontitis. | The 3020insC mutation of the /"NOD2"///"CARD15"/ gene in patients with periodontal disease. | The 3020insC mutation of the /"NOD2"///"CARD15"/ gene leads to impaired activation of nuclear factor-kappa B (NF-kappaB) in vitro. As the destruction of periodontal tissue is mediated via activation of NF-kappaB, with subsequent transcription of proinflammatory cytokines, the c-insertion mutation of the /"NOD2"///"CARD15"/ gene might contribute to the proposed genetic background of /"periodontitis"/. The present study analysed the frequency of this mutation in 80 patients with chronic periodontal disease and 122 healthy controls. The 3020insC mutation was identified by employing the polymerase chain reaction followed by restriction fragment length polymorphism analysis. The prevalence of the 3020insC mutation of the /"NOD2"///"CARD15"/ protein in patients with /"periodontitis"/ was 1.9% (three of 160) and that for the control group was 2.0% (five of 244) (P = 0.942). Hence, unlike in Crohn's disease, the 3020insC mutation of the /"NOD2"///"CARD15"/ gene does not seem to influence the pathophysiology of /"periodontitis"/. | [
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15279649 | The 3020insC mutation of the NOD2/CARD15 gene in patients with periodontal disease. | The 3020insC mutation of the NOD2/CARD15 gene leads to impaired activation of nuclear factor-kappa B (NF-kappaB) in vitro. As the destruction of periodontal tissue is mediated via activation of NF-kappaB, with subsequent transcription of proinflammatory cytokines, the c-insertion mutation of the NOD2/CARD15 gene might contribute to the proposed genetic background of periodontitis. The present study analysed the frequency of this mutation in 80 patients with chronic periodontal disease and 122 healthy controls. The 3020insC mutation was identified by employing the polymerase chain reaction followed by restriction fragment length polymorphism analysis. The prevalence of the 3020insC mutation of the NOD2/CARD15 protein in patients with periodontitis was 1.9% (three of 160) and that for the control group was 2.0% (five of 244) (P = 0.942). Hence, unlike in Crohn's disease, the 3020insC mutation of the NOD2/CARD15 gene does not seem to influence the pathophysiology of periodontitis. | The 3020insC mutation of the /"NOD2"///"CARD15"/ gene in patients with /"periodontal disease"/. | The 3020insC mutation of the /"NOD2"///"CARD15"/ gene leads to impaired activation of nuclear factor-kappa B (NF-kappaB) in vitro. As the destruction of periodontal tissue is mediated via activation of NF-kappaB, with subsequent transcription of proinflammatory cytokines, the c-insertion mutation of the /"NOD2"///"CARD15"/ gene might contribute to the proposed genetic background of periodontitis. The present study analysed the frequency of this mutation in 80 patients with chronic periodontal disease and 122 healthy controls. The 3020insC mutation was identified by employing the polymerase chain reaction followed by restriction fragment length polymorphism analysis. The prevalence of the 3020insC mutation of the /"NOD2"///"CARD15"/ protein in patients with periodontitis was 1.9% (three of 160) and that for the control group was 2.0% (five of 244) (P = 0.942). Hence, unlike in Crohn's disease, the 3020insC mutation of the /"NOD2"///"CARD15"/ gene does not seem to influence the pathophysiology of periodontitis. | [
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15286153 | Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction. | We mapped a human deafness locus DFNB36 to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in ESPN, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of ESPN is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with ESPN mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. | Mutations of /"ESPN"/ cause autosomal recessive deafness and vestibular dysfunction. | We mapped a human /"deafness"/ locus /"DFNB36"/ to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in /"ESPN"/, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of /"ESPN"/ is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with /"ESPN"/ mutations will be a useful clinical marker for refining the differential diagnosis of /"non-syndromic deafness"/. | [
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15286153 | Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction. | We mapped a human deafness locus DFNB36 to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in ESPN, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of ESPN is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with ESPN mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. | Mutations of /"ESPN"/ cause autosomal recessive deafness and /"vestibular dysfunction"/. | We mapped a human deafness locus /"DFNB36"/ to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and /"vestibular areflexia"/. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in /"ESPN"/, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of /"ESPN"/ is known to cause hearing loss and /"vestibular dysfunction"/ in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with /"ESPN"/ mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. | [
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15286153 | Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction. | We mapped a human deafness locus DFNB36 to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in ESPN, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of ESPN is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with ESPN mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. | Mutations of /"ESPN"/ cause /"autosomal recessive deafness"/ and vestibular dysfunction. | We mapped a human deafness locus /"DFNB36"/ to chromosome 1p36.3 in two consanguineous families segregating /"recessively inherited deafness"/ and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in /"ESPN"/, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of /"ESPN"/ is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with /"ESPN"/ mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. | [
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15286153 | Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction. | We mapped a human deafness locus DFNB36 to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in ESPN, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of ESPN is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with ESPN mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. | Mutations of /"ESPN"/ cause autosomal recessive deafness and vestibular dysfunction. | We mapped a human deafness locus /"DFNB36"/ to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in /"ESPN"/, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of /"ESPN"/ is known to cause /"hearing loss"/ and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with /"ESPN"/ mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. | [
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15287851 | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between HFE mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common HFE mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of HFE mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between /"HFE"/ mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and /"hepatic fibrosis"/ (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common /"HFE"/ mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe /"hepatic fibrosis"/. Our findings support a role of /"HFE"/ mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | [
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15287851 | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between HFE mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common HFE mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of HFE mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in /"chronic hepatitis C"/. | BACKGROUND: /"Chronic hepatitis C"/ is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between /"HFE"/ mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common /"HFE"/ mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of /"HFE"/ mutations as primary risk factors for fibrogenesis and disease progression in /"chronic hepatitis C"/. | [
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15287851 | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between HFE mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common HFE mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of HFE mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | Common heterozygous /"hemochromatosis"/ gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of /"hemochromatosis"/ genes affect fibrosis progression. Therefore our aim was to assess associations between /"HFE"/ mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common /"HFE"/ mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous /"hemochromatosis"/ mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of /"HFE"/ mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | [
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15287851 | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between HFE mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common HFE mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of HFE mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in /"chronic hepatitis C"/. | BACKGROUND: /"Chronic hepatitis C"/ is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between HFE mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common HFE mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the /"transferrin receptor 2"/ gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of HFE mutations as primary risk factors for fibrogenesis and disease progression in /"chronic hepatitis C"/. | [
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15287851 | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between HFE mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common HFE mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of HFE mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between /"HFE"/ mutations and hepatic inflammation and stage of fibrosis in German /"hepatitis C"/ patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common /"HFE"/ mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of /"HFE"/ mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | [
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"text_name": "hemochromatosis"
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"entity_id": "D006526",
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"text_name": "hepatitis C"
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"text_name": "hepatic fibrosis"
},
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"entity_type": "Disease",
"text_name": "hepatic fibrosis"
},
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"entity_id": "D019698",
"entity_type": "Disease",
"text_name": "chronic hepatitis C"
},
{
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"entity_id": "D019698",
"entity_type": "Disease",
"text_name": "Chronic hepatitis C"
},
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"entity_id": "D019698",
"entity_type": "Disease",
"text_name": "chronic hepatitis C"
},
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"entity_type": "Gene",
"text_name": "A2-4"
},
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"entity_type": "Gene",
"text_name": "HFE"
},
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"entity_type": "Gene",
"text_name": "HFE"
},
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"entity_id": "3077",
"entity_type": "Gene",
"text_name": "HFE"
},
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"end_idx": "892",
"entity_id": "7036",
"entity_type": "Gene",
"text_name": "transferrin receptor 2"
}
] | {
"begin_idx": "378",
"end_idx": "381",
"entity_id": "3077",
"entity_type": "Gene",
"text_name": "HFE"
} | {
"begin_idx": "449",
"end_idx": "460",
"entity_id": "D006526",
"entity_type": "Disease",
"text_name": "hepatitis C"
} | No |
15287851 | Common heterozygous hemochromatosis gene mutations are risk factors for inflammation and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between HFE mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common HFE mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of HFE mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | Common heterozygous hemochromatosis gene mutations are risk factors for /"inflammation"/ and fibrosis in chronic hepatitis C. | BACKGROUND: Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between /"HFE"/ mutations and hepatic /"inflammation"/ and stage of fibrosis in German hepatitis C patients. METHODS: Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing. RESULTS: The frequencies of common /"HFE"/ mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01). CONCLUSIONS: Common heterozygous hemochromatosis mutations are associated with higher grades of /"inflammation"/ and more severe hepatic fibrosis. Our findings support a role of /"HFE"/ mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C. | [
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},
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}
] | {
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} | {
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"end_idx": "1699",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
} | No |
15292102 | Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population. | Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and ACE are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and ACE I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between ACE I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED. | Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for /"erectile dysfunction"/ in the Mexican Mestizo population. | Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and /"angiotensin-converting enzyme"/ (/"ACE"/) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of /"erectile dysfunction"/ (/"ED"/). Endothelial NOS and /"ACE"/ are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and /"ACE"/ I/D polymorphisms in Mexican patients with /"ED"/ (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of /"ED"/ (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for /"ED"/, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between /"ACE"/ I/D polymorphism and /"ED"/ in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for /"ED"/. | [
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"text_name": "endothelial nitric oxide synthase"
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} | {
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} | Yes |
15292102 | Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population. | Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and ACE are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and ACE I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between ACE I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED. | Glu298Asp /"endothelial nitric oxide synthase"/ polymorphism is a risk factor for /"erectile dysfunction"/ in the Mexican Mestizo population. | Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. /"Endothelial nitric oxide synthase"/ (eNOS) and angiotensin-converting enzyme (ACE) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of /"erectile dysfunction"/ (/"ED"/). Endothelial NOS and ACE are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and ACE I/D polymorphisms in Mexican patients with /"ED"/ (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of /"ED"/ (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for /"ED"/, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between ACE I/D polymorphism and /"ED"/ in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for /"ED"/. | [
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"text_name": "erectile dysfunction"
} | Yes |
15292102 | Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population. | Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and ACE are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and ACE I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between ACE I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED. | Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population. | Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and /"angiotensin-converting enzyme"/ (/"ACE"/) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and /"ACE"/ are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and /"ACE"/ I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, /"hypertension"/, cardiac disease, and cigarette smoking. No association was found between /"ACE"/ I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED. | [
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"text_name": "diabetes mellitus"
},
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"text_name": "angiotensin-converting enzyme"
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{
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"text_name": "endothelial nitric oxide synthase"
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{
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] | {
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} | No |
15292102 | Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population. | Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and ACE are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and ACE I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between ACE I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED. | Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population. | Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and /"angiotensin-converting enzyme"/ (/"ACE"/) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and /"ACE"/ are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and /"ACE"/ I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, hypertension, /"cardiac disease"/, and cigarette smoking. No association was found between /"ACE"/ I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED. | [
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{
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"entity_type": "Gene",
"text_name": "Endothelial nitric oxide synthase"
}
] | {
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} | {
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"end_idx": "1395",
"entity_id": "D006331",
"entity_type": "Disease",
"text_name": "cardiac disease"
} | No |
15300989 | Gene symbol: IRF6. Disease: Van der Woude syndrome. | Gene symbol: /"IRF6"/. Disease: /"Van der Woude syndrome"/. | [
{
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"entity_id": "C536528",
"entity_type": "Disease",
"text_name": "Van der Woude syndrome"
},
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"entity_id": "3664",
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}
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"entity_id": "C536528",
"entity_type": "Disease",
"text_name": "Van der Woude syndrome"
} | Yes |
||
15307921 | Rapid determination of the Delta32 deletion in the human CC-chemokine receptor 5 (CCR5) gene without DNA extraction by lightcycler real-time polymerase chain reaction. | CCR5 is a major coreceptor for cellular entry of macrophage-tropic isolates of the human immunodeficiency virus (HIV). A 32-base pair deletion of the CCR5 gene (CCR5Delta32) protects against HIV infection because the frame shift leads to a truncated protein not expressed on the cell surface. CCR5Delta32 also delays progression in heterozygous HIV-infected patients and improves responses to antiretroviral therapy. Available methods for CCR5 genotyping, however, are cost expensive and/or time consuming. To improve CCR5 genotyping we studied four primer sets flanking the CCR5Delta32 deletion site using real-time polymerase chain reaction (PCR) on a LightCycler device. Primers amplified fragments of different length depending on the presence or absence of the Delta32 mutation. Next, melting curves of the amplified fragments were analyzed using SYBR green, a conventional double-strand DNA dye. To circumvent initial DNA extraction, we also studied serially diluted "interphase" leukocytes as PCR templates after centrifugation of EDTA blood. Finally, the validity of the new method was checked by analyzing 100 blood samples with known CCR5 genotypes. Amplicons of 82 bp:50 bp and 97 bp:65 bp fragment ratios could easily be discriminated due to the differences in their melting temperatures (3 degrees C and 2 degrees C, respectively). Furthermore, CCR5 genotyping was possible without initial DNA extraction and yielded optimal results at 1:400 to 1:600 dilution of the "interphase" leukocytes. Results of the new LightCycler PCR protocol were identical to conventional CCR5 genotyping but required considerably less time and expenditures. We have established a new real-time PCR protocol, which enables fast, cost-saving, and reliable CCR5 genotyping. | Rapid determination of the Delta32 deletion in the human /"CC-chemokine receptor 5"/ (/"CCR5"/) gene without DNA extraction by lightcycler real-time polymerase chain reaction. | /"CCR5"/ is a major coreceptor for cellular entry of macrophage-tropic isolates of the /"human immunodeficiency virus"/ (/"HIV"/). A 32-base pair deletion of the /"CCR5"/ gene (CCR5Delta32) protects against /"HIV infection"/ because the frame shift leads to a truncated protein not expressed on the cell surface. CCR5Delta32 also delays progression in heterozygous /"HIV-infected"/ patients and improves responses to antiretroviral therapy. Available methods for /"CCR5"/ genotyping, however, are cost expensive and/or time consuming. To improve /"CCR5"/ genotyping we studied four primer sets flanking the CCR5Delta32 deletion site using real-time polymerase chain reaction (PCR) on a LightCycler device. Primers amplified fragments of different length depending on the presence or absence of the Delta32 mutation. Next, melting curves of the amplified fragments were analyzed using SYBR green, a conventional double-strand DNA dye. To circumvent initial DNA extraction, we also studied serially diluted "interphase" leukocytes as PCR templates after centrifugation of EDTA blood. Finally, the validity of the new method was checked by analyzing 100 blood samples with known /"CCR5"/ genotypes. Amplicons of 82 bp:50 bp and 97 bp:65 bp fragment ratios could easily be discriminated due to the differences in their melting temperatures (3 degrees C and 2 degrees C, respectively). Furthermore, /"CCR5"/ genotyping was possible without initial DNA extraction and yielded optimal results at 1:400 to 1:600 dilution of the "interphase" leukocytes. Results of the new LightCycler PCR protocol were identical to conventional /"CCR5"/ genotyping but required considerably less time and expenditures. We have established a new real-time PCR protocol, which enables fast, cost-saving, and reliable /"CCR5"/ genotyping. | [
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"text_name": "human immunodeficiency virus"
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} | {
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"end_idx": "279",
"entity_id": "D015658",
"entity_type": "Disease",
"text_name": "human immunodeficiency virus"
} | Yes |
15308589 | Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers. | We reported previously that subjects homozygous for the cytochrome P450 2A6 (CYP2A6) (*)4 have a lower risk of lung cancer. The purpose of this study was to clarify whether or not the alterations of smoking behavior and risk for lung cancer could be found in subjects possessing novel CYP2A6 variants discovered recently. An epidemiological study was performed with 1094 cases and 611 controls in male Japanese smokers. It was found that the amounts of daily cigarette consumption in subjects who harbored CYP2A6(*)4/(*)7, (*)4/(*)10, (*)7/(*)7, (*)7/(*)9 and (*)4/(*)4 genotypes were significantly less than those in subjects carrying the (*)1/(*)1 genotype (P < 0.01). Even after adjustment with cigarette consumption, the adjusted odds ratios (ORs) for lung cancer were significantly lower in subjects who harbored CYP2A6(*)1/(*)4, (*)1/(*)7, (*)1/(*)9, (*)1/(*)10, (*)4/(*)4, (*)4/(*)7, (*)4/(*)9, (*)7/(*)7 and (*)7/(*)9 genotypes than those who possessed the (*)1/(*)1 genotype (P < 0.05). When participants were classified into four groups according to the CYP2A6 genotypes, group 1 ((*)1/(*)1), group 2 (heterozygotes for the (*)1 and a variant allele), group 3 (heterozygotes and homozygotes for variant alleles except for (*)4/(*)4) and group 4 ((*)4/(*)4), lung cancer risk was found to be less in subjects with the variant of CYP2A6 alleles [group 2, OR of 0.59 [95% confidence interval (CI), 0.44-0.79]; group 3, OR of 0.52 (95% CI, 0.37-0.72); group 4, OR of 0.30 (95% CI, 0.16-0.57)]. The reduced risk for lung cancer was seen more clearly in heavy smokers than in light smokers. Additional stratification analysis showed that the ORs for squamous cell carcinoma (OR of 0.07) and small cell carcinoma (OR of 0.10) were lower than that of adenocarcinoma (OR of 0.39) in group 4. These results suggest that the CYP2A6 is one of the principal determinants affecting not only smoking behavior but also susceptibility to tobacco-related lung cancer. | Evaluation of /"CYP2A6"/ genetic polymorphisms as determinants of smoking behavior and tobacco-related /"lung cancer"/ risk in male Japanese smokers. | We reported previously that subjects homozygous for the cytochrome P450 2A6 (/"CYP2A6"/) (*)4 have a lower risk of /"lung cancer"/. The purpose of this study was to clarify whether or not the alterations of smoking behavior and risk for /"lung cancer"/ could be found in subjects possessing novel /"CYP2A6"/ variants discovered recently. An epidemiological study was performed with 1094 cases and 611 controls in male Japanese smokers. It was found that the amounts of daily cigarette consumption in subjects who harbored /"CYP2A6"/(*)4/(*)7, (*)4/(*)10, (*)7/(*)7, (*)7/(*)9 and (*)4/(*)4 genotypes were significantly less than those in subjects carrying the (*)1/(*)1 genotype (P < 0.01). Even after adjustment with cigarette consumption, the adjusted odds ratios (ORs) for /"lung cancer"/ were significantly lower in subjects who harbored /"CYP2A6"/(*)1/(*)4, (*)1/(*)7, (*)1/(*)9, (*)1/(*)10, (*)4/(*)4, (*)4/(*)7, (*)4/(*)9, (*)7/(*)7 and (*)7/(*)9 genotypes than those who possessed the (*)1/(*)1 genotype (P < 0.05). When participants were classified into four groups according to the /"CYP2A6"/ genotypes, group 1 ((*)1/(*)1), group 2 (heterozygotes for the (*)1 and a variant allele), group 3 (heterozygotes and homozygotes for variant alleles except for (*)4/(*)4) and group 4 ((*)4/(*)4), /"lung cancer"/ risk was found to be less in subjects with the variant of /"CYP2A6"/ alleles [group 2, OR of 0.59 [95% confidence interval (CI), 0.44-0.79]; group 3, OR of 0.52 (95% CI, 0.37-0.72); group 4, OR of 0.30 (95% CI, 0.16-0.57)]. The reduced risk for /"lung cancer"/ was seen more clearly in heavy smokers than in light smokers. Additional stratification analysis showed that the ORs for squamous cell carcinoma (OR of 0.07) and small cell carcinoma (OR of 0.10) were lower than that of adenocarcinoma (OR of 0.39) in group 4. These results suggest that the /"CYP2A6"/ is one of the principal determinants affecting not only smoking behavior but also susceptibility to tobacco-related /"lung cancer"/. | [
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] | {
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} | {
"begin_idx": "99",
"end_idx": "110",
"entity_id": "D008175",
"entity_type": "Disease",
"text_name": "lung cancer"
} | Yes |
15308589 | Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers. | We reported previously that subjects homozygous for the cytochrome P450 2A6 (CYP2A6) (*)4 have a lower risk of lung cancer. The purpose of this study was to clarify whether or not the alterations of smoking behavior and risk for lung cancer could be found in subjects possessing novel CYP2A6 variants discovered recently. An epidemiological study was performed with 1094 cases and 611 controls in male Japanese smokers. It was found that the amounts of daily cigarette consumption in subjects who harbored CYP2A6(*)4/(*)7, (*)4/(*)10, (*)7/(*)7, (*)7/(*)9 and (*)4/(*)4 genotypes were significantly less than those in subjects carrying the (*)1/(*)1 genotype (P < 0.01). Even after adjustment with cigarette consumption, the adjusted odds ratios (ORs) for lung cancer were significantly lower in subjects who harbored CYP2A6(*)1/(*)4, (*)1/(*)7, (*)1/(*)9, (*)1/(*)10, (*)4/(*)4, (*)4/(*)7, (*)4/(*)9, (*)7/(*)7 and (*)7/(*)9 genotypes than those who possessed the (*)1/(*)1 genotype (P < 0.05). When participants were classified into four groups according to the CYP2A6 genotypes, group 1 ((*)1/(*)1), group 2 (heterozygotes for the (*)1 and a variant allele), group 3 (heterozygotes and homozygotes for variant alleles except for (*)4/(*)4) and group 4 ((*)4/(*)4), lung cancer risk was found to be less in subjects with the variant of CYP2A6 alleles [group 2, OR of 0.59 [95% confidence interval (CI), 0.44-0.79]; group 3, OR of 0.52 (95% CI, 0.37-0.72); group 4, OR of 0.30 (95% CI, 0.16-0.57)]. The reduced risk for lung cancer was seen more clearly in heavy smokers than in light smokers. Additional stratification analysis showed that the ORs for squamous cell carcinoma (OR of 0.07) and small cell carcinoma (OR of 0.10) were lower than that of adenocarcinoma (OR of 0.39) in group 4. These results suggest that the CYP2A6 is one of the principal determinants affecting not only smoking behavior but also susceptibility to tobacco-related lung cancer. | Evaluation of /"CYP2A6"/ genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers. | We reported previously that subjects homozygous for the cytochrome P450 2A6 (/"CYP2A6"/) (*)4 have a lower risk of lung cancer. The purpose of this study was to clarify whether or not the alterations of smoking behavior and risk for lung cancer could be found in subjects possessing novel /"CYP2A6"/ variants discovered recently. An epidemiological study was performed with 1094 cases and 611 controls in male Japanese smokers. It was found that the amounts of daily cigarette consumption in subjects who harbored /"CYP2A6"/(*)4/(*)7, (*)4/(*)10, (*)7/(*)7, (*)7/(*)9 and (*)4/(*)4 genotypes were significantly less than those in subjects carrying the (*)1/(*)1 genotype (P < 0.01). Even after adjustment with cigarette consumption, the adjusted odds ratios (ORs) for lung cancer were significantly lower in subjects who harbored /"CYP2A6"/(*)1/(*)4, (*)1/(*)7, (*)1/(*)9, (*)1/(*)10, (*)4/(*)4, (*)4/(*)7, (*)4/(*)9, (*)7/(*)7 and (*)7/(*)9 genotypes than those who possessed the (*)1/(*)1 genotype (P < 0.05). When participants were classified into four groups according to the /"CYP2A6"/ genotypes, group 1 ((*)1/(*)1), group 2 (heterozygotes for the (*)1 and a variant allele), group 3 (heterozygotes and homozygotes for variant alleles except for (*)4/(*)4) and group 4 ((*)4/(*)4), lung cancer risk was found to be less in subjects with the variant of /"CYP2A6"/ alleles [group 2, OR of 0.59 [95% confidence interval (CI), 0.44-0.79]; group 3, OR of 0.52 (95% CI, 0.37-0.72); group 4, OR of 0.30 (95% CI, 0.16-0.57)]. The reduced risk for lung cancer was seen more clearly in heavy smokers than in light smokers. Additional stratification analysis showed that the ORs for squamous cell carcinoma (OR of 0.07) and /"small cell carcinoma"/ (OR of 0.10) were lower than that of adenocarcinoma (OR of 0.39) in group 4. These results suggest that the /"CYP2A6"/ is one of the principal determinants affecting not only smoking behavior but also susceptibility to tobacco-related lung cancer. | [
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15308875 | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | Influence of cytokine gene polymorphisms on /"focal segmental glomerulosclerosis"/. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of /"TGF-beta(1)"/ gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of /"focal segmental glomerulosclerosis"/ (/"FSGS"/). METHODS: The clinical course of 71 patients with biopsy-proven primary /"FSGS"/ followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of /"FSGS"/ as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that /"TGF-beta(1)"/ gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in /"focal segmental glomerulosclerosis"/. | [
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15308875 | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | Influence of cytokine gene polymorphisms on /"focal segmental glomerulosclerosis"/. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, /"TNF alpha"/ gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of /"focal segmental glomerulosclerosis"/ (/"FSGS"/). METHODS: The clinical course of 71 patients with biopsy-proven primary /"FSGS"/ followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of /"FSGS"/ as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, /"TNF alpha"/ gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in /"focal segmental glomerulosclerosis"/. | [
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15308875 | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | Influence of cytokine gene polymorphisms on /"focal segmental glomerulosclerosis"/. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and /"IL-6"/ gene G-174C polymorphisms on the clinical manifestations of /"focal segmental glomerulosclerosis"/ (/"FSGS"/). METHODS: The clinical course of 71 patients with biopsy-proven primary /"FSGS"/ followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of /"FSGS"/ as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and /"IL-6"/ gene G-174C polymorphisms are not risk factors or markers of progression in /"focal segmental glomerulosclerosis"/. | [
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15308875 | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and /"IL-6"/ gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, /"proteinuria"/ and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and /"IL-6"/ gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | [
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15308875 | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of /"TGF-beta(1)"/ gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, /"proteinuria"/ and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that /"TGF-beta(1)"/ gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | [
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15308875 | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, proteinuria and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and IL-6 gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | Influence of cytokine gene polymorphisms on focal segmental glomerulosclerosis. | BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and /"IL-6"/ gene G-174C polymorphisms on the clinical manifestations of focal segmental glomerulosclerosis (FSGS). METHODS: The clinical course of 71 patients with biopsy-proven primary FSGS followed up for 6.0 +/- 4.4 years was studied. Patients were classified according to the slope of reciprocal serum creatinine into slow (n = 49) and fast (n = 22) progressors. One hundred healthy volunteers were analysed as controls. Genetic polymorphisms were determined by PCR amplification. RESULTS: The genotype distribution of the studied polymorphisms was similar in patients and controls (n.s.). Age, initial renal function, /"proteinuria"/ and blood pressure did not differ significantly between patients with different genotypes (n.s.). The investigated polymorphisms were not associated with the progression of FSGS as shown by the similar genotype frequencies among slow and fast progressors (n.s.) and the renal survival in the Kaplan-Meier analysis (n.s.). CONCLUSION: Our results indicate that TGF-beta(1) gene Arg(25)-->Pro, TNF alpha gene G-308A and /"IL-6"/ gene G-174C polymorphisms are not risk factors or markers of progression in focal segmental glomerulosclerosis. | [
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15318030 | Allelic association analysis of phospholipase A2 genes with schizophrenia. | Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for schizophrenia in our sample; however, confirmatory studies in independent samples are needed. | Allelic association analysis of phospholipase A2 genes with /"schizophrenia"/. | Several studies suggest increased activity of phospholipase A2 in /"schizophrenic"/ patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, /"iPLA2"/ and PAFAH) were analysed in a case-control sample using 240 /"schizophrenic"/ patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the /"iPLA2"/ gene polymorphism was found. In conclusion, our data suggested that /"iPLA2"/ may play a role as a susceptibility gene for /"schizophrenia"/ in our sample; however, confirmatory studies in independent samples are needed. | [
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15318030 | Allelic association analysis of phospholipase A2 genes with schizophrenia. | Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for schizophrenia in our sample; however, confirmatory studies in independent samples are needed. | Allelic association analysis of phospholipase A2 genes with /"schizophrenia"/. | Several studies suggest increased activity of phospholipase A2 in /"schizophrenic"/ patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and /"PAFAH"/) were analysed in a case-control sample using 240 /"schizophrenic"/ patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The /"PAFAH"/ variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for /"schizophrenia"/ in our sample; however, confirmatory studies in independent samples are needed. | [
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15318030 | Allelic association analysis of phospholipase A2 genes with schizophrenia. | Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for schizophrenia in our sample; however, confirmatory studies in independent samples are needed. | Allelic association analysis of phospholipase A2 genes with /"schizophrenia"/. | Several studies suggest increased activity of phospholipase A2 in /"schizophrenic"/ patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, /"cPLA2"/, iPLA2 and PAFAH) were analysed in a case-control sample using 240 /"schizophrenic"/ patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of /"cPLA2"/ and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for /"schizophrenia"/ in our sample; however, confirmatory studies in independent samples are needed. | [
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15318030 | Allelic association analysis of phospholipase A2 genes with schizophrenia. | Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for schizophrenia in our sample; however, confirmatory studies in independent samples are needed. | Allelic association analysis of phospholipase A2 genes with /"schizophrenia"/. | Several studies suggest increased activity of phospholipase A2 in /"schizophrenic"/ patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (/"sPLA2"/, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 /"schizophrenic"/ patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and /"sPLA2"/ gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for /"schizophrenia"/ in our sample; however, confirmatory studies in independent samples are needed. | [
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15318030 | Allelic association analysis of phospholipase A2 genes with schizophrenia. | Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for schizophrenia in our sample; however, confirmatory studies in independent samples are needed. | Allelic association analysis of /"phospholipase A2"/ genes with /"schizophrenia"/. | Several studies suggest increased activity of /"phospholipase A2"/ in /"schizophrenic"/ patients. In the present study, variants of four genes coding for /"phospholipase A2"/ enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 /"schizophrenic"/ patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for /"schizophrenia"/ in our sample; however, confirmatory studies in independent samples are needed. | [
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15318030 | Allelic association analysis of phospholipase A2 genes with schizophrenia. | Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for schizophrenia in our sample; however, confirmatory studies in independent samples are needed. | Allelic association analysis of /"phospholipase A2"/ genes with /"schizophrenia"/. | Several studies suggest increased activity of /"phospholipase A2"/ in /"schizophrenic"/ patients. In the present study, variants of four genes coding for /"phospholipase A2"/ enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 /"schizophrenic"/ patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for /"schizophrenia"/ in our sample; however, confirmatory studies in independent samples are needed. | [
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15318030 | Allelic association analysis of phospholipase A2 genes with schizophrenia. | Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for schizophrenia in our sample; however, confirmatory studies in independent samples are needed. | Allelic association analysis of /"phospholipase A2"/ genes with /"schizophrenia"/. | Several studies suggest increased activity of /"phospholipase A2"/ in /"schizophrenic"/ patients. In the present study, variants of four genes coding for /"phospholipase A2"/ enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 /"schizophrenic"/ patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for /"schizophrenia"/ in our sample; however, confirmatory studies in independent samples are needed. | [
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15318030 | Allelic association analysis of phospholipase A2 genes with schizophrenia. | Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for schizophrenia in our sample; however, confirmatory studies in independent samples are needed. | Allelic association analysis of /"phospholipase A2"/ genes with /"schizophrenia"/. | Several studies suggest increased activity of /"phospholipase A2"/ in /"schizophrenic"/ patients. In the present study, variants of four genes coding for /"phospholipase A2"/ enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 /"schizophrenic"/ patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups. The PAFAH variant was very rare in our population and therefore not informative. A significant allelic (chi2=5.86, P=0.0085, odds ratio=1.38, 95% confidence interval, 1.08-1.77) and genotypic (chi2=5.4, P=0.02) association with the iPLA2 gene polymorphism was found. In conclusion, our data suggested that iPLA2 may play a role as a susceptibility gene for /"schizophrenia"/ in our sample; however, confirmatory studies in independent samples are needed. | [
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15320482 | [NOD2/CARD15 mutations and genotype-phenotype correlations in patients with Crohn's disease. Hungarian multicenter study]. | Recently mutations of the NOD2/CARD15 gene were identified as genetic markers for Crohn's disease (CD). It has also been suggested that the presence of mutation may influence the phenotype of the disease. The aim of this study was to determine the frequency of common NOD2/CARD15 mutations in Hungarian Crohn's patients. PATIENTS AND METHODS: DNA was obtained from 142 pts with Crohn's disease (70 male and 72 female, mean age: 36.2 yrs) and of 115 healthy subjects. Clinical data were obtained by filling in a questionnaire by the physician. DNA was screened for possible mutations by denaturing HPLC (WAVE Nucleic acid fragment analysis systems, Cheshire, UK) using published primers (Lesage et al, Am J Hum Gen 2002) for SNP's 8, 12, and 13. Mutations were then confirmed by direct sequencing on a ABI Prism 310 Genetic Analyzer (Perkin Elmer; Norwalk, USA). RESULTS: Mutations of NOD2/CARD15 were significantly more frequent in patients (n = 42, 29.6%) than in controls (11.3%, p = 0.0007, OR = 3.3, 95% CI = 1.7-6.5). R702W and 3020insC mutations were significantly more common in IBD compared to controls (4.3% and 2.6%); 18 patients had the R702W mutation (12.7%, p = 0.001, 13 homozygous, one homozygous for R703C) and 22 the 3020insC (15.9%, p = 0.001, 4 homozygous). 7 patients (4.9%) were heterozygous for the G908R, which was not different from the controls (4.3%). 5 patients were compound heterozygous. The allele frequency of R702W (11.6% vs. 4.3%, p = 0.0026, OR = 5.9, 95% CI: 2.3-14.9) and 3020insC (9.1% vs. 2.6% p = 0.004, OR = 7.6, 95% CI = 2.4-24.0) was significantly higher in Crohn's disease compared to the controls. Age at presentation was not different between carriers and non-carriers (26.7 +/- [SD] 10.3 yrs vs. 27.7 +/- 11.8 yrs). There was a tendency of ileal location to be more common in carriers of the mutation (40.5% vs. 29.0%), while colonic location was less frequent (16.7% vs. 44%). The presence of the mutation did not affect disease behaviour (carrier: inflammatory: 30.9%, stenosing: 26.2%, penetrating: 42.9%, non-carrier: inflammatory: 36%, stenosing: 27%, penetrating: 37%). Among the extraintestinal manifestations arthritis (30.1% vs. 47%, p = 0.05) and primary sclerosing cholangitis (0% vs. 9%, p = 0.047%) was significantly less frequent in carriers of the mutation. CONCLUSIONS: In concordance with European data we found a high number of NOD2/CARD15 R702W and 3020insC mutations in Hungarian patients with Crohn's disease. The G908R mutation was uncommon in Hungarian Crohn's patients. The presence of the mutation was associated with ileal but not with fibrostenosing disease and extraintestinal manifestations were less common in carriers of the mutation. | [/"NOD2"///"CARD15"/ mutations and genotype-phenotype correlations in patients with /"Crohn's disease"/. Hungarian multicenter study]. | Recently mutations of the /"NOD2"///"CARD15"/ gene were identified as genetic markers for /"Crohn's disease"/ (/"CD"/). It has also been suggested that the presence of mutation may influence the phenotype of the disease. The aim of this study was to determine the frequency of common /"NOD2"///"CARD15"/ mutations in Hungarian /"Crohn's"/ patients. PATIENTS AND METHODS: DNA was obtained from 142 pts with /"Crohn's disease"/ (70 male and 72 female, mean age: 36.2 yrs) and of 115 healthy subjects. Clinical data were obtained by filling in a questionnaire by the physician. DNA was screened for possible mutations by denaturing HPLC (WAVE Nucleic acid fragment analysis systems, Cheshire, UK) using published primers (Lesage et al, Am J Hum Gen 2002) for SNP's 8, 12, and 13. Mutations were then confirmed by direct sequencing on a ABI Prism 310 Genetic Analyzer (Perkin Elmer; Norwalk, USA). RESULTS: Mutations of /"NOD2"///"CARD15"/ were significantly more frequent in patients (n = 42, 29.6%) than in controls (11.3%, p = 0.0007, OR = 3.3, 95% CI = 1.7-6.5). R702W and 3020insC mutations were significantly more common in IBD compared to controls (4.3% and 2.6%); 18 patients had the R702W mutation (12.7%, p = 0.001, 13 homozygous, one homozygous for R703C) and 22 the 3020insC (15.9%, p = 0.001, 4 homozygous). 7 patients (4.9%) were heterozygous for the G908R, which was not different from the controls (4.3%). 5 patients were compound heterozygous. The allele frequency of R702W (11.6% vs. 4.3%, p = 0.0026, OR = 5.9, 95% CI: 2.3-14.9) and 3020insC (9.1% vs. 2.6% p = 0.004, OR = 7.6, 95% CI = 2.4-24.0) was significantly higher in /"Crohn's disease"/ compared to the controls. Age at presentation was not different between carriers and non-carriers (26.7 +/- [SD] 10.3 yrs vs. 27.7 +/- 11.8 yrs). There was a tendency of ileal location to be more common in carriers of the mutation (40.5% vs. 29.0%), while colonic location was less frequent (16.7% vs. 44%). The presence of the mutation did not affect disease behaviour (carrier: inflammatory: 30.9%, stenosing: 26.2%, penetrating: 42.9%, non-carrier: inflammatory: 36%, stenosing: 27%, penetrating: 37%). Among the extraintestinal manifestations arthritis (30.1% vs. 47%, p = 0.05) and primary sclerosing cholangitis (0% vs. 9%, p = 0.047%) was significantly less frequent in carriers of the mutation. CONCLUSIONS: In concordance with European data we found a high number of /"NOD2"///"CARD15"/ R702W and 3020insC mutations in Hungarian patients with /"Crohn's disease"/. The G908R mutation was uncommon in Hungarian /"Crohn's"/ patients. The presence of the mutation was associated with ileal but not with fibrostenosing disease and extraintestinal manifestations were less common in carriers of the mutation. | [
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15320482 | [NOD2/CARD15 mutations and genotype-phenotype correlations in patients with Crohn's disease. Hungarian multicenter study]. | Recently mutations of the NOD2/CARD15 gene were identified as genetic markers for Crohn's disease (CD). It has also been suggested that the presence of mutation may influence the phenotype of the disease. The aim of this study was to determine the frequency of common NOD2/CARD15 mutations in Hungarian Crohn's patients. PATIENTS AND METHODS: DNA was obtained from 142 pts with Crohn's disease (70 male and 72 female, mean age: 36.2 yrs) and of 115 healthy subjects. Clinical data were obtained by filling in a questionnaire by the physician. DNA was screened for possible mutations by denaturing HPLC (WAVE Nucleic acid fragment analysis systems, Cheshire, UK) using published primers (Lesage et al, Am J Hum Gen 2002) for SNP's 8, 12, and 13. Mutations were then confirmed by direct sequencing on a ABI Prism 310 Genetic Analyzer (Perkin Elmer; Norwalk, USA). RESULTS: Mutations of NOD2/CARD15 were significantly more frequent in patients (n = 42, 29.6%) than in controls (11.3%, p = 0.0007, OR = 3.3, 95% CI = 1.7-6.5). R702W and 3020insC mutations were significantly more common in IBD compared to controls (4.3% and 2.6%); 18 patients had the R702W mutation (12.7%, p = 0.001, 13 homozygous, one homozygous for R703C) and 22 the 3020insC (15.9%, p = 0.001, 4 homozygous). 7 patients (4.9%) were heterozygous for the G908R, which was not different from the controls (4.3%). 5 patients were compound heterozygous. The allele frequency of R702W (11.6% vs. 4.3%, p = 0.0026, OR = 5.9, 95% CI: 2.3-14.9) and 3020insC (9.1% vs. 2.6% p = 0.004, OR = 7.6, 95% CI = 2.4-24.0) was significantly higher in Crohn's disease compared to the controls. Age at presentation was not different between carriers and non-carriers (26.7 +/- [SD] 10.3 yrs vs. 27.7 +/- 11.8 yrs). There was a tendency of ileal location to be more common in carriers of the mutation (40.5% vs. 29.0%), while colonic location was less frequent (16.7% vs. 44%). The presence of the mutation did not affect disease behaviour (carrier: inflammatory: 30.9%, stenosing: 26.2%, penetrating: 42.9%, non-carrier: inflammatory: 36%, stenosing: 27%, penetrating: 37%). Among the extraintestinal manifestations arthritis (30.1% vs. 47%, p = 0.05) and primary sclerosing cholangitis (0% vs. 9%, p = 0.047%) was significantly less frequent in carriers of the mutation. CONCLUSIONS: In concordance with European data we found a high number of NOD2/CARD15 R702W and 3020insC mutations in Hungarian patients with Crohn's disease. The G908R mutation was uncommon in Hungarian Crohn's patients. The presence of the mutation was associated with ileal but not with fibrostenosing disease and extraintestinal manifestations were less common in carriers of the mutation. | [/"NOD2"///"CARD15"/ mutations and genotype-phenotype correlations in patients with Crohn's disease. Hungarian multicenter study]. | Recently mutations of the /"NOD2"///"CARD15"/ gene were identified as genetic markers for Crohn's disease (CD). It has also been suggested that the presence of mutation may influence the phenotype of the disease. The aim of this study was to determine the frequency of common /"NOD2"///"CARD15"/ mutations in Hungarian Crohn's patients. PATIENTS AND METHODS: DNA was obtained from 142 pts with Crohn's disease (70 male and 72 female, mean age: 36.2 yrs) and of 115 healthy subjects. Clinical data were obtained by filling in a questionnaire by the physician. DNA was screened for possible mutations by denaturing HPLC (WAVE Nucleic acid fragment analysis systems, Cheshire, UK) using published primers (Lesage et al, Am J Hum Gen 2002) for SNP's 8, 12, and 13. Mutations were then confirmed by direct sequencing on a ABI Prism 310 Genetic Analyzer (Perkin Elmer; Norwalk, USA). RESULTS: Mutations of /"NOD2"///"CARD15"/ were significantly more frequent in patients (n = 42, 29.6%) than in controls (11.3%, p = 0.0007, OR = 3.3, 95% CI = 1.7-6.5). R702W and 3020insC mutations were significantly more common in /"IBD"/ compared to controls (4.3% and 2.6%); 18 patients had the R702W mutation (12.7%, p = 0.001, 13 homozygous, one homozygous for R703C) and 22 the 3020insC (15.9%, p = 0.001, 4 homozygous). 7 patients (4.9%) were heterozygous for the G908R, which was not different from the controls (4.3%). 5 patients were compound heterozygous. The allele frequency of R702W (11.6% vs. 4.3%, p = 0.0026, OR = 5.9, 95% CI: 2.3-14.9) and 3020insC (9.1% vs. 2.6% p = 0.004, OR = 7.6, 95% CI = 2.4-24.0) was significantly higher in Crohn's disease compared to the controls. Age at presentation was not different between carriers and non-carriers (26.7 +/- [SD] 10.3 yrs vs. 27.7 +/- 11.8 yrs). There was a tendency of ileal location to be more common in carriers of the mutation (40.5% vs. 29.0%), while colonic location was less frequent (16.7% vs. 44%). The presence of the mutation did not affect disease behaviour (carrier: inflammatory: 30.9%, stenosing: 26.2%, penetrating: 42.9%, non-carrier: inflammatory: 36%, stenosing: 27%, penetrating: 37%). Among the extraintestinal manifestations arthritis (30.1% vs. 47%, p = 0.05) and primary sclerosing cholangitis (0% vs. 9%, p = 0.047%) was significantly less frequent in carriers of the mutation. CONCLUSIONS: In concordance with European data we found a high number of /"NOD2"///"CARD15"/ R702W and 3020insC mutations in Hungarian patients with Crohn's disease. The G908R mutation was uncommon in Hungarian Crohn's patients. The presence of the mutation was associated with ileal but not with fibrostenosing disease and extraintestinal manifestations were less common in carriers of the mutation. | [
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15375002 | A functional polymorphism in RGS6 modulates the risk of bladder cancer. | RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study. | A functional polymorphism in RGS6 modulates the risk of /"bladder cancer"/. | RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 /"bladder cancer"/ patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in /"RGS2"/ and RGS6 were each associated with a statistically significant reduction in /"bladder cancer"/ risk. The risk of /"bladder cancer"/ was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of /"bladder cancer"/ (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that /"RGS2"/ transcripts and several splice variants of RGS6 are expressed in /"bladder cancer"/ cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study. | [
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} | Yes |
15375002 | A functional polymorphism in RGS6 modulates the risk of bladder cancer. | RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study. | A functional polymorphism in /"RGS6"/ modulates the risk of /"bladder cancer"/. | RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 /"bladder cancer"/ patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and /"RGS6"/ were each associated with a statistically significant reduction in /"bladder cancer"/ risk. The risk of /"bladder cancer"/ was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the /"RGS6"/-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of /"bladder cancer"/ (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the /"RGS6"/-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of /"RGS6"/ are expressed in /"bladder cancer"/ cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate /"RGS6"/ as a target for further study. | [
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"entity_id": "D001749",
"entity_type": "Disease",
"text_name": "bladder cancer"
} | Yes |
15375002 | A functional polymorphism in RGS6 modulates the risk of bladder cancer. | RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study. | A functional polymorphism in RGS6 modulates the risk of /"bladder cancer"/. | /"RGS"/ proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that /"RGS"/ proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 /"bladder cancer"/ patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in /"bladder cancer"/ risk. The risk of /"bladder cancer"/ was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of /"bladder cancer"/ (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-/"RGS"/ fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in /"bladder cancer"/ cells. These data provide the first evidence that /"RGS"/ proteins may be important modulators of cancer risk and validate RGS6 as a target for further study. | [
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"entity_id": "D001749",
"entity_type": "Disease",
"text_name": "bladder cancer"
} | No |
15375002 | A functional polymorphism in RGS6 modulates the risk of bladder cancer. | RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study. | A functional polymorphism in RGS6 modulates the risk of bladder cancer. | RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in /"RGS2"/ and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that /"RGS2"/ transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of /"cancer"/ risk and validate RGS6 as a target for further study. | [
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} | {
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} | No |
15380041 | Estrogen receptor-alpha gene haplotype is associated with primary knee osteoarthritis in Korean population. | Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-alpha gene polymorphisms for its associations with primary knee OA, we conducted a case-control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-alpha gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-alpha gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01-1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, chi2 = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-alpha gene haplotype may be associated with primary knee OA, and genetic variations in the ER-alpha gene may be involved in OA. | /"Estrogen receptor-alpha"/ gene haplotype is associated with primary /"knee osteoarthritis"/ in Korean population. | Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate /"ER-alpha"/ gene polymorphisms for its associations with primary knee OA, we conducted a case-control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the /"ER-alpha"/ gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the /"ER-alpha"/ gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01-1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, chi2 = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that /"ER-alpha"/ gene haplotype may be associated with primary knee OA, and genetic variations in the /"ER-alpha"/ gene may be involved in OA. | [
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} | Yes |
15380041 | Estrogen receptor-alpha gene haplotype is associated with primary knee osteoarthritis in Korean population. | Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-alpha gene polymorphisms for its associations with primary knee OA, we conducted a case-control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-alpha gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-alpha gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01-1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, chi2 = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-alpha gene haplotype may be associated with primary knee OA, and genetic variations in the ER-alpha gene may be involved in OA. | /"Estrogen receptor-alpha"/ gene haplotype is associated with primary knee osteoarthritis in Korean population. | Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of /"osteoarthritis"/ (/"OA"/). To investigate /"ER-alpha"/ gene polymorphisms for its associations with primary knee /"OA"/, we conducted a case-control association study in patients with primary knee /"OA"/ (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the /"ER-alpha"/ gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee /"OA"/. Genotypes of the /"ER-alpha"/ gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee /"OA"/ patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee /"OA"/ patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01-1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee /"OA"/ patients and control individuals (degrees of freedom = 7, chi2 = 21.48; P = 0.003). Although the /"number OA"/ patients studied is small, the present study shows that /"ER-alpha"/ gene haplotype may be associated with primary knee /"OA"/, and genetic variations in the /"ER-alpha"/ gene may be involved in /"OA"/. | [
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"text_name": "OA"
} | No |
15386943 | Interaction and relationship between angiotensin converting enzyme gene and environmental factors predisposing to essential hypertension in Mongolian population of China. | OBJECTIVE: To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. METHODS: Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. RESULTS: The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short,there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect CONCLUSION: It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention. | Interaction and relationship between /"angiotensin converting enzyme"/ gene and environmental factors predisposing to essential /"hypertension"/ in Mongolian population of China. | OBJECTIVE: To investigate the association of specific functional gene /"ACE"/ (I/D) variants of the renin-angiotensin system with essential /"hypertension"/ (EH) and interaction between /"ACE"/ (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. METHODS: Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. RESULTS: The association was found between /"ACE"/ genotype DD plus ID and EH, with an interaction between /"ACE"/ genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and /"ACE"/ gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between /"ACE"/ genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and /"ACE"/ gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and /"ACE"/ gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between /"ACE"/ genotype and WHR on EH showed a multiplicative model. In a short,there was an interaction between /"ACE"/ gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect CONCLUSION: It is important for individuals who carry /"ACE"/ D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention. | [
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"entity_type": "Disease",
"text_name": "hypertension"
} | Yes |
15386943 | Interaction and relationship between angiotensin converting enzyme gene and environmental factors predisposing to essential hypertension in Mongolian population of China. | OBJECTIVE: To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. METHODS: Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. RESULTS: The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short,there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect CONCLUSION: It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention. | Interaction and relationship between /"angiotensin converting enzyme"/ gene and environmental factors predisposing to essential hypertension in Mongolian population of China. | OBJECTIVE: To investigate the association of specific functional gene /"ACE"/ (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between /"ACE"/ (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. METHODS: Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. RESULTS: The association was found between /"ACE"/ genotype DD plus ID and EH, with an interaction between /"ACE"/ genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and /"ACE"/ gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between /"ACE"/ genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and /"ACE"/ gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and /"ACE"/ gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between /"ACE"/ genotype and WHR on EH showed a multiplicative model. In a short,there was an interaction between /"ACE"/ gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect CONCLUSION: It is important for individuals who carry /"ACE"/ D allele gene to prevent EH, and furthermore, to prevent and control /"coronary heart disease"/, in a view of population-based prevention. | [
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"text_name": "coronary heart disease"
} | No |
15459589 | Short alleles of P-selectin glycoprotein ligand-1 protect against premature myocardial infarction. | BACKGROUND: Atherosclerosis is an inflammatory disease resulting from an injury that leads to an increase in the adhesiveness and permeability of the endothelium to leukocytes or platelets. The selectin family plays a key role initiating the cascade of events. Recently, we have demonstrated the functional relevance of a variable number of tandem repeats polymorphism affecting the P-selectin glycoprotein ligand (PSGL-1). Neutrophils carrying short alleles exhibit a significantly lower capacity to bind activated platelets. These alleles consistently protect against transient ischemic attack. We sought to evaluate the role of this polymorphism in premature myocardial infarction because genetic risk factors have more relevance in the development of disease in young patients. METHODS: We genotyped 219 Caucasian patients who had suffered a premature myocardial infarction (MI) (aged < or =45 years) and 594 control subjects from our Mediterranean area. The role of the PSGL-1 polymorphism was also evaluated according to the additional risk factors of age, sex, smoking history, hypertension, hypercholesterolemia, and diabetes. RESULTS: The frequency of the short alleles (B and C) was significantly lower in patients than in controls (P =.012, odds ratio 0.62; 95% CI 0.42-0.92). Multiple regression analysis revealed that B and C alleles had an independent protective effect on the development of premature MI (P =.034, odds ratio 0.62 95%CI: 0.40-0.96). CONCLUSIONS: We found an interesting association between a functional polymorphism and the risk of MI at a younger age. According to our results, the short B and C PSGL-1 alleles might protect against premature MI, probably because of their lesser adhesive capacity. | Short alleles of /"P-selectin glycoprotein ligand"/-1 protect against premature /"myocardial infarction"/. | BACKGROUND: Atherosclerosis is an inflammatory disease resulting from an injury that leads to an increase in the adhesiveness and permeability of the endothelium to leukocytes or platelets. The selectin family plays a key role initiating the cascade of events. Recently, we have demonstrated the functional relevance of a variable number of tandem repeats polymorphism affecting the /"P-selectin glycoprotein ligand"/ (/"PSGL-1"/). Neutrophils carrying short alleles exhibit a significantly lower capacity to bind activated platelets. These alleles consistently protect against transient ischemic attack. We sought to evaluate the role of this polymorphism in premature /"myocardial infarction"/ because genetic risk factors have more relevance in the development of disease in young patients. METHODS: We genotyped 219 Caucasian patients who had suffered a premature /"myocardial infarction"/ (/"MI"/) (aged < or =45 years) and 594 control subjects from our Mediterranean area. The role of the /"PSGL-1"/ polymorphism was also evaluated according to the additional risk factors of age, sex, smoking history, hypertension, hypercholesterolemia, and diabetes. RESULTS: The frequency of the short alleles (B and C) was significantly lower in patients than in controls (P =.012, odds ratio 0.62; 95% CI 0.42-0.92). Multiple regression analysis revealed that B and C alleles had an independent protective effect on the development of /"premature MI"/ (P =.034, odds ratio 0.62 95%CI: 0.40-0.96). CONCLUSIONS: We found an interesting association between a functional polymorphism and the risk of /"MI"/ at a younger age. According to our results, the short B and C /"PSGL-1"/ alleles might protect against /"premature MI"/, probably because of their lesser adhesive capacity. | [
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"text_name": "myocardial infarction"
} | Yes |
15459589 | Short alleles of P-selectin glycoprotein ligand-1 protect against premature myocardial infarction. | BACKGROUND: Atherosclerosis is an inflammatory disease resulting from an injury that leads to an increase in the adhesiveness and permeability of the endothelium to leukocytes or platelets. The selectin family plays a key role initiating the cascade of events. Recently, we have demonstrated the functional relevance of a variable number of tandem repeats polymorphism affecting the P-selectin glycoprotein ligand (PSGL-1). Neutrophils carrying short alleles exhibit a significantly lower capacity to bind activated platelets. These alleles consistently protect against transient ischemic attack. We sought to evaluate the role of this polymorphism in premature myocardial infarction because genetic risk factors have more relevance in the development of disease in young patients. METHODS: We genotyped 219 Caucasian patients who had suffered a premature myocardial infarction (MI) (aged < or =45 years) and 594 control subjects from our Mediterranean area. The role of the PSGL-1 polymorphism was also evaluated according to the additional risk factors of age, sex, smoking history, hypertension, hypercholesterolemia, and diabetes. RESULTS: The frequency of the short alleles (B and C) was significantly lower in patients than in controls (P =.012, odds ratio 0.62; 95% CI 0.42-0.92). Multiple regression analysis revealed that B and C alleles had an independent protective effect on the development of premature MI (P =.034, odds ratio 0.62 95%CI: 0.40-0.96). CONCLUSIONS: We found an interesting association between a functional polymorphism and the risk of MI at a younger age. According to our results, the short B and C PSGL-1 alleles might protect against premature MI, probably because of their lesser adhesive capacity. | Short alleles of /"P-selectin glycoprotein ligand"/-1 protect against premature myocardial infarction. | BACKGROUND: Atherosclerosis is an inflammatory disease resulting from an injury that leads to an increase in the adhesiveness and permeability of the endothelium to leukocytes or platelets. The selectin family plays a key role initiating the cascade of events. Recently, we have demonstrated the functional relevance of a variable number of tandem repeats polymorphism affecting the /"P-selectin glycoprotein ligand"/ (/"PSGL-1"/). Neutrophils carrying short alleles exhibit a significantly lower capacity to bind activated platelets. These alleles consistently protect against transient ischemic attack. We sought to evaluate the role of this polymorphism in premature myocardial infarction because genetic risk factors have more relevance in the development of disease in young patients. METHODS: We genotyped 219 Caucasian patients who had suffered a premature myocardial infarction (MI) (aged < or =45 years) and 594 control subjects from our Mediterranean area. The role of the /"PSGL-1"/ polymorphism was also evaluated according to the additional risk factors of age, sex, smoking history, hypertension, hypercholesterolemia, and /"diabetes"/. RESULTS: The frequency of the short alleles (B and C) was significantly lower in patients than in controls (P =.012, odds ratio 0.62; 95% CI 0.42-0.92). Multiple regression analysis revealed that B and C alleles had an independent protective effect on the development of premature MI (P =.034, odds ratio 0.62 95%CI: 0.40-0.96). CONCLUSIONS: We found an interesting association between a functional polymorphism and the risk of MI at a younger age. According to our results, the short B and C /"PSGL-1"/ alleles might protect against premature MI, probably because of their lesser adhesive capacity. | [
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"entity_id": "D003920",
"entity_type": "Disease",
"text_name": "diabetes"
} | No |
15466944 | Hyperhomocysteinemia, enzyme polymorphism and thiobarbituric Acid reactive system in children with high coronary risk family history. | OBJECTIVES: To investigate both the frequency and the genetic background of hyperhomocysteinemia and the frequency of increased plasma thiobarbituric acid reactive system (TBARS) levels in children and adolescents whose parents had premature coronary heart disease (CHD). METHODS: The study was performed on children and adolescents aged 4-18 years (105 offspring of parents with CHD before age 45 and 74 referents from families without any evidence of premature atherosclerosis). Fasting serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and total triglyceride (TG) levels were measured by enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was measured by fluorescence polarisation immunoassay. Plasma TBARS level was determined by fluorimetric method. 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme polymorphism was analyzed by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). RESULTS: Hyperhomocysteinemia was found in 32 cases and in 4 controls. Increased plasma THCy level was found in 10 children and adolescents from 12 cases homozygous for the C677T polymorphism of the MTHFR gene. No similar high frequency was observed in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38 cases and in 8 controls. The frequency differences were significant (p < 0.01). Allele frequency of the MTHFR polymorphism among cases and controls was similar. Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and all other children had normal serum TC, LDL-C, HDL-C and TG levels from children with hyperhomocysteinemia and/or high plasma TBARS levels. A significant correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of parents and children in the case group. CONCLUSION: The measurement of plasma THCy and TBARS levels may contribute to the detection of the risk of children and adolescents with high CHD risk family history. | Hyperhomocysteinemia, enzyme polymorphism and thiobarbituric Acid reactive system in children with high coronary risk family history. | OBJECTIVES: To investigate both the frequency and the genetic background of hyperhomocysteinemia and the frequency of increased plasma thiobarbituric acid reactive system (TBARS) levels in children and adolescents whose parents had premature /"coronary heart disease"/ (/"CHD"/). METHODS: The study was performed on children and adolescents aged 4-18 years (105 offspring of parents with /"CHD"/ before age 45 and 74 referents from families without any evidence of premature atherosclerosis). Fasting serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and total triglyceride (TG) levels were measured by enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was measured by fluorescence polarisation immunoassay. Plasma TBARS level was determined by fluorimetric method. /"5,10-methylenetetrahydrofolate reductase"/ (/"MTHFR"/) enzyme polymorphism was analyzed by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). RESULTS: Hyperhomocysteinemia was found in 32 cases and in 4 controls. Increased plasma THCy level was found in 10 children and adolescents from 12 cases homozygous for the C677T polymorphism of the /"MTHFR"/ gene. No similar high frequency was observed in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38 cases and in 8 controls. The frequency differences were significant (p < 0.01). Allele frequency of the /"MTHFR"/ polymorphism among cases and controls was similar. Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and all other children had normal serum TC, LDL-C, HDL-C and TG levels from children with hyperhomocysteinemia and/or high plasma TBARS levels. A significant correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of parents and children in the case group. CONCLUSION: The measurement of plasma THCy and TBARS levels may contribute to the detection of the risk of children and adolescents with high /"CHD"/ risk family history. | [
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"entity_type": "Disease",
"text_name": "coronary heart disease"
} | Yes |
15466944 | Hyperhomocysteinemia, enzyme polymorphism and thiobarbituric Acid reactive system in children with high coronary risk family history. | OBJECTIVES: To investigate both the frequency and the genetic background of hyperhomocysteinemia and the frequency of increased plasma thiobarbituric acid reactive system (TBARS) levels in children and adolescents whose parents had premature coronary heart disease (CHD). METHODS: The study was performed on children and adolescents aged 4-18 years (105 offspring of parents with CHD before age 45 and 74 referents from families without any evidence of premature atherosclerosis). Fasting serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and total triglyceride (TG) levels were measured by enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was measured by fluorescence polarisation immunoassay. Plasma TBARS level was determined by fluorimetric method. 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme polymorphism was analyzed by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). RESULTS: Hyperhomocysteinemia was found in 32 cases and in 4 controls. Increased plasma THCy level was found in 10 children and adolescents from 12 cases homozygous for the C677T polymorphism of the MTHFR gene. No similar high frequency was observed in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38 cases and in 8 controls. The frequency differences were significant (p < 0.01). Allele frequency of the MTHFR polymorphism among cases and controls was similar. Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and all other children had normal serum TC, LDL-C, HDL-C and TG levels from children with hyperhomocysteinemia and/or high plasma TBARS levels. A significant correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of parents and children in the case group. CONCLUSION: The measurement of plasma THCy and TBARS levels may contribute to the detection of the risk of children and adolescents with high CHD risk family history. | /"Hyperhomocysteinemia"/, enzyme polymorphism and thiobarbituric Acid reactive system in children with high coronary risk family history. | OBJECTIVES: To investigate both the frequency and the genetic background of /"hyperhomocysteinemia"/ and the frequency of increased plasma thiobarbituric acid reactive system (TBARS) levels in children and adolescents whose parents had premature coronary heart disease (CHD). METHODS: The study was performed on children and adolescents aged 4-18 years (105 offspring of parents with CHD before age 45 and 74 referents from families without any evidence of premature atherosclerosis). Fasting serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and total triglyceride (TG) levels were measured by enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was measured by fluorescence polarisation immunoassay. Plasma TBARS level was determined by fluorimetric method. /"5,10-methylenetetrahydrofolate reductase"/ (/"MTHFR"/) enzyme polymorphism was analyzed by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). RESULTS: /"Hyperhomocysteinemia"/ was found in 32 cases and in 4 controls. Increased plasma THCy level was found in 10 children and adolescents from 12 cases homozygous for the C677T polymorphism of the /"MTHFR"/ gene. No similar high frequency was observed in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38 cases and in 8 controls. The frequency differences were significant (p < 0.01). Allele frequency of the /"MTHFR"/ polymorphism among cases and controls was similar. Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and all other children had normal serum TC, LDL-C, HDL-C and TG levels from children with /"hyperhomocysteinemia"/ and/or high plasma TBARS levels. A significant correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of parents and children in the case group. CONCLUSION: The measurement of plasma THCy and TBARS levels may contribute to the detection of the risk of children and adolescents with high CHD risk family history. | [
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} | Yes |
15466944 | Hyperhomocysteinemia, enzyme polymorphism and thiobarbituric Acid reactive system in children with high coronary risk family history. | OBJECTIVES: To investigate both the frequency and the genetic background of hyperhomocysteinemia and the frequency of increased plasma thiobarbituric acid reactive system (TBARS) levels in children and adolescents whose parents had premature coronary heart disease (CHD). METHODS: The study was performed on children and adolescents aged 4-18 years (105 offspring of parents with CHD before age 45 and 74 referents from families without any evidence of premature atherosclerosis). Fasting serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and total triglyceride (TG) levels were measured by enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was measured by fluorescence polarisation immunoassay. Plasma TBARS level was determined by fluorimetric method. 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme polymorphism was analyzed by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). RESULTS: Hyperhomocysteinemia was found in 32 cases and in 4 controls. Increased plasma THCy level was found in 10 children and adolescents from 12 cases homozygous for the C677T polymorphism of the MTHFR gene. No similar high frequency was observed in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38 cases and in 8 controls. The frequency differences were significant (p < 0.01). Allele frequency of the MTHFR polymorphism among cases and controls was similar. Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and all other children had normal serum TC, LDL-C, HDL-C and TG levels from children with hyperhomocysteinemia and/or high plasma TBARS levels. A significant correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of parents and children in the case group. CONCLUSION: The measurement of plasma THCy and TBARS levels may contribute to the detection of the risk of children and adolescents with high CHD risk family history. | Hyperhomocysteinemia, enzyme polymorphism and thiobarbituric Acid reactive system in children with high coronary risk family history. | OBJECTIVES: To investigate both the frequency and the genetic background of hyperhomocysteinemia and the frequency of increased plasma thiobarbituric acid reactive system (TBARS) levels in children and adolescents whose parents had premature coronary heart disease (CHD). METHODS: The study was performed on children and adolescents aged 4-18 years (105 offspring of parents with CHD before age 45 and 74 referents from families without any evidence of /"premature atherosclerosis"/). Fasting serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and total triglyceride (TG) levels were measured by enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was measured by fluorescence polarisation immunoassay. Plasma TBARS level was determined by fluorimetric method. /"5,10-methylenetetrahydrofolate reductase"/ (/"MTHFR"/) enzyme polymorphism was analyzed by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). RESULTS: Hyperhomocysteinemia was found in 32 cases and in 4 controls. Increased plasma THCy level was found in 10 children and adolescents from 12 cases homozygous for the C677T polymorphism of the /"MTHFR"/ gene. No similar high frequency was observed in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38 cases and in 8 controls. The frequency differences were significant (p < 0.01). Allele frequency of the /"MTHFR"/ polymorphism among cases and controls was similar. Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and all other children had normal serum TC, LDL-C, HDL-C and TG levels from children with hyperhomocysteinemia and/or high plasma TBARS levels. A significant correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of parents and children in the case group. CONCLUSION: The measurement of plasma THCy and TBARS levels may contribute to the detection of the risk of children and adolescents with high CHD risk family history. | [
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} | {
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"text_name": "premature atherosclerosis"
} | No |
15466944 | Hyperhomocysteinemia, enzyme polymorphism and thiobarbituric Acid reactive system in children with high coronary risk family history. | OBJECTIVES: To investigate both the frequency and the genetic background of hyperhomocysteinemia and the frequency of increased plasma thiobarbituric acid reactive system (TBARS) levels in children and adolescents whose parents had premature coronary heart disease (CHD). METHODS: The study was performed on children and adolescents aged 4-18 years (105 offspring of parents with CHD before age 45 and 74 referents from families without any evidence of premature atherosclerosis). Fasting serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and total triglyceride (TG) levels were measured by enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was measured by fluorescence polarisation immunoassay. Plasma TBARS level was determined by fluorimetric method. 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme polymorphism was analyzed by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). RESULTS: Hyperhomocysteinemia was found in 32 cases and in 4 controls. Increased plasma THCy level was found in 10 children and adolescents from 12 cases homozygous for the C677T polymorphism of the MTHFR gene. No similar high frequency was observed in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38 cases and in 8 controls. The frequency differences were significant (p < 0.01). Allele frequency of the MTHFR polymorphism among cases and controls was similar. Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and all other children had normal serum TC, LDL-C, HDL-C and TG levels from children with hyperhomocysteinemia and/or high plasma TBARS levels. A significant correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of parents and children in the case group. CONCLUSION: The measurement of plasma THCy and TBARS levels may contribute to the detection of the risk of children and adolescents with high CHD risk family history. | Hyperhomocysteinemia, enzyme polymorphism and thiobarbituric Acid reactive system in children with high coronary risk family history. | OBJECTIVES: To investigate both the frequency and the genetic background of hyperhomocysteinemia and the frequency of increased plasma thiobarbituric acid reactive system (TBARS) levels in children and adolescents whose parents had premature coronary heart disease (CHD). METHODS: The study was performed on children and adolescents aged 4-18 years (105 offspring of parents with CHD before age 45 and 74 referents from families without any evidence of /"premature atherosclerosis"/). Fasting serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and total triglyceride (TG) levels were measured by enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was measured by fluorescence polarisation immunoassay. Plasma TBARS level was determined by fluorimetric method. /"5,10-methylenetetrahydrofolate reductase"/ (/"MTHFR"/) enzyme polymorphism was analyzed by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). RESULTS: Hyperhomocysteinemia was found in 32 cases and in 4 controls. Increased plasma THCy level was found in 10 children and adolescents from 12 cases homozygous for the C677T polymorphism of the /"MTHFR"/ gene. No similar high frequency was observed in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38 cases and in 8 controls. The frequency differences were significant (p < 0.01). Allele frequency of the /"MTHFR"/ polymorphism among cases and controls was similar. Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and all other children had normal serum TC, LDL-C, HDL-C and TG levels from children with hyperhomocysteinemia and/or high plasma TBARS levels. A significant correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of parents and children in the case group. CONCLUSION: The measurement of plasma THCy and TBARS levels may contribute to the detection of the risk of children and adolescents with high CHD risk family history. | [
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15472214 | Lack of an association between peroxisome proliferator-activated receptor-gamma gene Pro12Ala polymorphism and adiponectin levels in the polycystic ovary syndrome. | Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic diseases and is characterized by obesity in approximately 50% of those affected. Adiponectin is an adipocyte-derived protein that possesses an antiatherosclerotic action and improves insulin sensitivity. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) regulates the transcription of several adipocyte-specific genes. The aim of this study was to investigate the putative influence of the PPAR-gamma gene Pro12Ala polymorphism on the adiponectin levels in PCOS and healthy women. One hundred twenty women with PCOS and 120 healthy women whose ages and body mass indexes matched those of the PCOS patients were investigated. The genetic analysis of PPAR-gamma gene Pro12Ala polymorphism was performed by restriction fragment of polymorphisms. Serum adiponectin levels were evaluated, and the homeostasis model assessment score was also calculated. No subject was homozygous for the Ala12 allele of the PPAR-gamma gene. No significant differences in body mass index, plasma glucose and lipid levels, and homeostasis model assessment scores were observed between and within genotype groups in PCOS and control women. No significant differences in serum adiponectin concentrations were observed between and within genotype groups in PCOS and control women. In conclusion, our results confirm that adiponectin concentrations are similar in PCOS and controls and demonstrate no effect of the PPAR-gamma gene Pro12Ala polymorphism on serum adiponectin levels. | Lack of an association between /"peroxisome proliferator-activated receptor-gamma"/ gene Pro12Ala polymorphism and adiponectin levels in the /"polycystic ovary syndrome"/. | /"Polycystic ovary syndrome"/ (/"PCOS"/) is one of the most common endocrine metabolic diseases and is characterized by obesity in approximately 50% of those affected. Adiponectin is an adipocyte-derived protein that possesses an antiatherosclerotic action and improves insulin sensitivity. /"Peroxisome proliferator-activated receptor-gamma"/ (/"PPAR-gamma"/) regulates the transcription of several adipocyte-specific genes. The aim of this study was to investigate the putative influence of the /"PPAR-gamma"/ gene Pro12Ala polymorphism on the adiponectin levels in /"PCOS"/ and healthy women. One hundred twenty women with /"PCOS"/ and 120 healthy women whose ages and body mass indexes matched those of the /"PCOS"/ patients were investigated. The genetic analysis of /"PPAR-gamma"/ gene Pro12Ala polymorphism was performed by restriction fragment of polymorphisms. Serum adiponectin levels were evaluated, and the homeostasis model assessment score was also calculated. No subject was homozygous for the Ala12 allele of the /"PPAR-gamma"/ gene. No significant differences in body mass index, plasma glucose and lipid levels, and homeostasis model assessment scores were observed between and within genotype groups in /"PCOS"/ and control women. No significant differences in serum adiponectin concentrations were observed between and within genotype groups in /"PCOS"/ and control women. In conclusion, our results confirm that adiponectin concentrations are similar in /"PCOS"/ and controls and demonstrate no effect of the /"PPAR-gamma"/ gene Pro12Ala polymorphism on serum adiponectin levels. | [
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15472214 | Lack of an association between peroxisome proliferator-activated receptor-gamma gene Pro12Ala polymorphism and adiponectin levels in the polycystic ovary syndrome. | Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic diseases and is characterized by obesity in approximately 50% of those affected. Adiponectin is an adipocyte-derived protein that possesses an antiatherosclerotic action and improves insulin sensitivity. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) regulates the transcription of several adipocyte-specific genes. The aim of this study was to investigate the putative influence of the PPAR-gamma gene Pro12Ala polymorphism on the adiponectin levels in PCOS and healthy women. One hundred twenty women with PCOS and 120 healthy women whose ages and body mass indexes matched those of the PCOS patients were investigated. The genetic analysis of PPAR-gamma gene Pro12Ala polymorphism was performed by restriction fragment of polymorphisms. Serum adiponectin levels were evaluated, and the homeostasis model assessment score was also calculated. No subject was homozygous for the Ala12 allele of the PPAR-gamma gene. No significant differences in body mass index, plasma glucose and lipid levels, and homeostasis model assessment scores were observed between and within genotype groups in PCOS and control women. No significant differences in serum adiponectin concentrations were observed between and within genotype groups in PCOS and control women. In conclusion, our results confirm that adiponectin concentrations are similar in PCOS and controls and demonstrate no effect of the PPAR-gamma gene Pro12Ala polymorphism on serum adiponectin levels. | Lack of an association between /"peroxisome proliferator-activated receptor-gamma"/ gene Pro12Ala polymorphism and adiponectin levels in the polycystic ovary syndrome. | Polycystic ovary syndrome (PCOS) is one of the most common endocrine /"metabolic diseases"/ and is characterized by obesity in approximately 50% of those affected. Adiponectin is an adipocyte-derived protein that possesses an antiatherosclerotic action and improves insulin sensitivity. /"Peroxisome proliferator-activated receptor-gamma"/ (/"PPAR-gamma"/) regulates the transcription of several adipocyte-specific genes. The aim of this study was to investigate the putative influence of the /"PPAR-gamma"/ gene Pro12Ala polymorphism on the adiponectin levels in PCOS and healthy women. One hundred twenty women with PCOS and 120 healthy women whose ages and body mass indexes matched those of the PCOS patients were investigated. The genetic analysis of /"PPAR-gamma"/ gene Pro12Ala polymorphism was performed by restriction fragment of polymorphisms. Serum adiponectin levels were evaluated, and the homeostasis model assessment score was also calculated. No subject was homozygous for the Ala12 allele of the /"PPAR-gamma"/ gene. No significant differences in body mass index, plasma glucose and lipid levels, and homeostasis model assessment scores were observed between and within genotype groups in PCOS and control women. No significant differences in serum adiponectin concentrations were observed between and within genotype groups in PCOS and control women. In conclusion, our results confirm that adiponectin concentrations are similar in PCOS and controls and demonstrate no effect of the /"PPAR-gamma"/ gene Pro12Ala polymorphism on serum adiponectin levels. | [
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