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16154235 | Association study of the vascular endothelial growth factor gene with the risk of developing Alzheimer's disease. | Numerous observations indicate that cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in AD. Converging evidence points to a pivotal role for vascular endothelial growth factor (VEGF) in neuronal protection, and the lack of activity of this in neurodegenerative disorders. The VEGF gene is located at 6p21.3, a site several studies have shown to have significant linkage with AD, and a functional polymorphism within the VEGF promoter may alter the risk of developing AD. We assessed the potential impact of this polymorphism on the risk of developing AD in a large French case-control population, and investigated its association with the severity of brain vascular lesions (arteriosclerosis, white matter loss and cerebral amyloid angiopathy) in several brain regions (frontal, temporal, parietal and occipital cortex) in AD. No association of the VEGF promoter polymorphism with the risk of developing AD was observed. No relationship between this polymorphism and vascular pathological changes in AD was detected. Our data indicate that although this polymorphism is functional, it does not confer greater risk for AD, nor modulate the extent of vascular pathology. | Association study of the /"vascular endothelial growth factor"/ gene with the risk of developing Alzheimer's disease. | Numerous observations indicate that cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in AD. Converging evidence points to a pivotal role for /"vascular endothelial growth factor"/ (/"VEGF"/) in neuronal protection, and the lack of activity of this in neurodegenerative disorders. The /"VEGF"/ gene is located at 6p21.3, a site several studies have shown to have significant linkage with AD, and a functional polymorphism within the /"VEGF"/ promoter may alter the risk of developing AD. We assessed the potential impact of this polymorphism on the risk of developing AD in a large French case-control population, and investigated its association with the severity of brain /"vascular lesions"/ (arteriosclerosis, white matter loss and cerebral amyloid angiopathy) in several brain regions (frontal, temporal, parietal and occipital cortex) in AD. No association of the /"VEGF"/ promoter polymorphism with the risk of developing AD was observed. No relationship between this polymorphism and vascular pathological changes in AD was detected. Our data indicate that although this polymorphism is functional, it does not confer greater risk for AD, nor modulate the extent of vascular pathology. | [
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16154235 | Association study of the vascular endothelial growth factor gene with the risk of developing Alzheimer's disease. | Numerous observations indicate that cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in AD. Converging evidence points to a pivotal role for vascular endothelial growth factor (VEGF) in neuronal protection, and the lack of activity of this in neurodegenerative disorders. The VEGF gene is located at 6p21.3, a site several studies have shown to have significant linkage with AD, and a functional polymorphism within the VEGF promoter may alter the risk of developing AD. We assessed the potential impact of this polymorphism on the risk of developing AD in a large French case-control population, and investigated its association with the severity of brain vascular lesions (arteriosclerosis, white matter loss and cerebral amyloid angiopathy) in several brain regions (frontal, temporal, parietal and occipital cortex) in AD. No association of the VEGF promoter polymorphism with the risk of developing AD was observed. No relationship between this polymorphism and vascular pathological changes in AD was detected. Our data indicate that although this polymorphism is functional, it does not confer greater risk for AD, nor modulate the extent of vascular pathology. | Association study of the /"vascular endothelial growth factor"/ gene with the risk of developing Alzheimer's disease. | Numerous observations indicate that cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in AD. Converging evidence points to a pivotal role for /"vascular endothelial growth factor"/ (/"VEGF"/) in neuronal protection, and the lack of activity of this in neurodegenerative disorders. The /"VEGF"/ gene is located at 6p21.3, a site several studies have shown to have significant linkage with AD, and a functional polymorphism within the /"VEGF"/ promoter may alter the risk of developing AD. We assessed the potential impact of this polymorphism on the risk of developing AD in a large French case-control population, and investigated its association with the severity of brain vascular lesions (/"arteriosclerosis"/, white matter loss and cerebral amyloid angiopathy) in several brain regions (frontal, temporal, parietal and occipital cortex) in AD. No association of the /"VEGF"/ promoter polymorphism with the risk of developing AD was observed. No relationship between this polymorphism and vascular pathological changes in AD was detected. Our data indicate that although this polymorphism is functional, it does not confer greater risk for AD, nor modulate the extent of vascular pathology. | [
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16154235 | Association study of the vascular endothelial growth factor gene with the risk of developing Alzheimer's disease. | Numerous observations indicate that cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in AD. Converging evidence points to a pivotal role for vascular endothelial growth factor (VEGF) in neuronal protection, and the lack of activity of this in neurodegenerative disorders. The VEGF gene is located at 6p21.3, a site several studies have shown to have significant linkage with AD, and a functional polymorphism within the VEGF promoter may alter the risk of developing AD. We assessed the potential impact of this polymorphism on the risk of developing AD in a large French case-control population, and investigated its association with the severity of brain vascular lesions (arteriosclerosis, white matter loss and cerebral amyloid angiopathy) in several brain regions (frontal, temporal, parietal and occipital cortex) in AD. No association of the VEGF promoter polymorphism with the risk of developing AD was observed. No relationship between this polymorphism and vascular pathological changes in AD was detected. Our data indicate that although this polymorphism is functional, it does not confer greater risk for AD, nor modulate the extent of vascular pathology. | Association study of the /"vascular endothelial growth factor"/ gene with the risk of developing Alzheimer's disease. | Numerous observations indicate that cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in AD. Converging evidence points to a pivotal role for /"vascular endothelial growth factor"/ (/"VEGF"/) in neuronal protection, and the lack of activity of this in neurodegenerative disorders. The /"VEGF"/ gene is located at 6p21.3, a site several studies have shown to have significant linkage with AD, and a functional polymorphism within the /"VEGF"/ promoter may alter the risk of developing AD. We assessed the potential impact of this polymorphism on the risk of developing AD in a large French case-control population, and investigated its association with the severity of brain vascular lesions (arteriosclerosis, white matter loss and /"cerebral amyloid angiopathy"/) in several brain regions (frontal, temporal, parietal and occipital cortex) in AD. No association of the /"VEGF"/ promoter polymorphism with the risk of developing AD was observed. No relationship between this polymorphism and vascular pathological changes in AD was detected. Our data indicate that although this polymorphism is functional, it does not confer greater risk for AD, nor modulate the extent of vascular pathology. | [
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16160007 | Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation. | Sequence analysis of the ADAMTS13 locus of 2 patients with hereditary thrombotic thrombocytopenic purpura (TTP) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of ADAMTS13 deficiency. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on ADAMTS13 secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced ADAMTS13-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of ADAMTS13 secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases. | Modulation of /"ADAMTS13"/ secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation. | Sequence analysis of the /"ADAMTS13"/ locus of 2 patients with hereditary /"thrombotic thrombocytopenic purpura"/ (/"TTP"/) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of ADAMTS13 deficiency. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on /"ADAMTS13"/ secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced /"ADAMTS13"/-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of /"ADAMTS13"/ secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases. | [
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16160007 | Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation. | Sequence analysis of the ADAMTS13 locus of 2 patients with hereditary thrombotic thrombocytopenic purpura (TTP) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of ADAMTS13 deficiency. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on ADAMTS13 secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced ADAMTS13-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of ADAMTS13 secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases. | Modulation of /"ADAMTS13"/ secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation. | Sequence analysis of the /"ADAMTS13"/ locus of 2 patients with hereditary thrombotic thrombocytopenic purpura (TTP) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of /"ADAMTS13 deficiency"/. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on /"ADAMTS13"/ secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced /"ADAMTS13"/-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of /"ADAMTS13"/ secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases. | [
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16167465 | Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence. | Dopamine D4 receptor (DRD4) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution. | Combined effect of promoter polymorphisms in the /"dopamine D4 receptor"/ and the serotonin transporter genes in /"heroin dependence"/. | /"Dopamine D4 receptor"/ (/"DRD4"/) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the /"DRD4"/ polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the /"DRD4"/ promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of /"DRD4"/ and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and /"heroin dependence"/ was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in /"heroin dependence"/. However, due to the limited size of our sample these results should be interpreted with caution. | [
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16167465 | Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence. | Dopamine D4 receptor (DRD4) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution. | Combined effect of promoter polymorphisms in the dopamine D4 receptor and the /"serotonin transporter"/ genes in /"heroin dependence"/. | Dopamine D4 receptor (DRD4) and /"serotonin transporter"/ (/"SERT"/) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the /"SERT"/ gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and /"heroin dependence"/ was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in /"heroin dependence"/. However, due to the limited size of our sample these results should be interpreted with caution. | [
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16167465 | Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence. | Dopamine D4 receptor (DRD4) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution. | Combined effect of promoter polymorphisms in the /"dopamine D4 receptor"/ and the serotonin transporter genes in heroin dependence. | /"Dopamine D4 receptor"/ (/"DRD4"/) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for /"substance dependence"/. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the /"DRD4"/ polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the /"DRD4"/ promoter region and /"substance dependence"/ was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of /"DRD4"/ and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution. | [
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} | No |
16167465 | Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence. | Dopamine D4 receptor (DRD4) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for substance dependence. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the DRD4 polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the DRD4 promoter region and substance dependence was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of DRD4 and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution. | Combined effect of promoter polymorphisms in the /"dopamine D4 receptor"/ and the serotonin transporter genes in heroin dependence. | /"Dopamine D4 receptor"/ (/"DRD4"/) and serotonin transporter (SERT) gene polymorphisms were studied, as possible genetic risk factors for /"substance dependence"/. The case-control study involved a large cohort (n = 362) of healthy Caucasian population, and an initial sample of 73 substance dependent patients (including a subgroup of 53 heroin dependents). Improved methods were applied for genotype detection of the /"DRD4"/ polymorphisms (exon 3 48 bp VNTR; -521 C/T SNP and 120 bp duplication in the 5' flanking region) and the SERT gene polymorphisms (5-hydroxytriptamin transporter linked polymorphic region [5-HTTLPR] in the 5' flanking region and the intron 2 VNTR [STin2]). Association between the -521 C/T SNP of the /"DRD4"/ promoter region and /"substance dependence"/ was significant in the subgroup of heroin dependents (p = 0.044). The other analyzed polymorphisms did not show any significant association, but an interaction between -521 C/T SNP of /"DRD4"/ and the 5-HTTLPR polymorphisms was observed. Association between the -521 CC vs. CT or TT genotypes and heroin dependence was enhanced in the presence of short (s or 14-repeat) 5-HTTLPR allele (p 0.01). The odds ratio of 2.14 observed for the -521 CC genotype increased to 4.82 in double homozygotes of -521 CC and 5-HTTLPR ss, emphasizing the importance of combined analysis of polymorphisms in the dopaminergic and serotonergic systems in heroin dependence. However, due to the limited size of our sample these results should be interpreted with caution. | [
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16168297 | Genetic polymorphism on endothelial nitric oxide synthase affects endothelial activation and inflammatory response during the acute phase of myocardial infarction. | OBJECTIVES: This study sought to evaluate the effect of genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS); on the risk for myocardial infarction (MI); and on the release of von Willebrand factor (vWF), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of MI and one year after the event. BACKGROUND: Genetic polymorphism G894T on eNOS has been associated with increased cardiovascular risk. However, its role during the acute phase of MI is unknown. METHODS: The study population consisted of 228 patients with a first event of premature MI and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year. RESULTS: The risk for MI in 894TT was 1.992 (95% confidence interval [CI], 1.131 to 3.485), p < 0.05 versus GG+GT; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% CI, 1.106 to 3.651), p < 0.05 versus GT. During the acute phase, vWF was higher in GT+TT (121.02 +/- 5.47%) versus GG (84.6 +/- 7.1%, p < 0.01), an effect persisting after one year (90.4 +/- 3.8 vs. 73.1 +/- 4.6%, p < 0.01). During the acute phase, GT+TT had higher ox-LDL and IL-6 (131.2 +/- 6.4 IU/l and 8.5 +/- 0.7 pg/ml) compared with GG (101.7 +/- 9.64 IU/l and 6.2 +/- 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year. CONCLUSIONS: G894T polymorphism on the eNOS gene increases the risk for premature MI and modifies the response of vascular endothelium during the acute phase of MI by affecting the release of vWF, IL-6, and oxidative stress status, an effect diminished one year after the event. | Genetic polymorphism on /"endothelial nitric oxide synthase"/ affects endothelial activation and inflammatory response during the acute phase of /"myocardial infarction"/. | OBJECTIVES: This study sought to evaluate the effect of genetic polymorphism G894T on /"endothelial nitric oxide synthase"/ (/"eNOS"/); on the risk for /"myocardial infarction"/ (/"MI"/); and on the release of von Willebrand factor (vWF), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of /"MI"/ and one year after the event. BACKGROUND: Genetic polymorphism G894T on /"eNOS"/ has been associated with increased cardiovascular risk. However, its role during the acute phase of /"MI"/ is unknown. METHODS: The study population consisted of 228 patients with a first event of premature /"MI"/ and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year. RESULTS: The risk for /"MI"/ in 894TT was 1.992 (95% confidence interval [CI], 1.131 to 3.485), p < 0.05 versus GG+GT; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% CI, 1.106 to 3.651), p < 0.05 versus GT. During the acute phase, vWF was higher in GT+TT (121.02 +/- 5.47%) versus GG (84.6 +/- 7.1%, p < 0.01), an effect persisting after one year (90.4 +/- 3.8 vs. 73.1 +/- 4.6%, p < 0.01). During the acute phase, GT+TT had higher ox-LDL and IL-6 (131.2 +/- 6.4 IU/l and 8.5 +/- 0.7 pg/ml) compared with GG (101.7 +/- 9.64 IU/l and 6.2 +/- 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year. CONCLUSIONS: G894T polymorphism on the /"eNOS"/ gene increases the risk for premature /"MI"/ and modifies the response of vascular endothelium during the acute phase of /"MI"/ by affecting the release of vWF, IL-6, and oxidative stress status, an effect diminished one year after the event. | [
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16168297 | Genetic polymorphism on endothelial nitric oxide synthase affects endothelial activation and inflammatory response during the acute phase of myocardial infarction. | OBJECTIVES: This study sought to evaluate the effect of genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS); on the risk for myocardial infarction (MI); and on the release of von Willebrand factor (vWF), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of MI and one year after the event. BACKGROUND: Genetic polymorphism G894T on eNOS has been associated with increased cardiovascular risk. However, its role during the acute phase of MI is unknown. METHODS: The study population consisted of 228 patients with a first event of premature MI and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year. RESULTS: The risk for MI in 894TT was 1.992 (95% confidence interval [CI], 1.131 to 3.485), p < 0.05 versus GG+GT; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% CI, 1.106 to 3.651), p < 0.05 versus GT. During the acute phase, vWF was higher in GT+TT (121.02 +/- 5.47%) versus GG (84.6 +/- 7.1%, p < 0.01), an effect persisting after one year (90.4 +/- 3.8 vs. 73.1 +/- 4.6%, p < 0.01). During the acute phase, GT+TT had higher ox-LDL and IL-6 (131.2 +/- 6.4 IU/l and 8.5 +/- 0.7 pg/ml) compared with GG (101.7 +/- 9.64 IU/l and 6.2 +/- 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year. CONCLUSIONS: G894T polymorphism on the eNOS gene increases the risk for premature MI and modifies the response of vascular endothelium during the acute phase of MI by affecting the release of vWF, IL-6, and oxidative stress status, an effect diminished one year after the event. | Genetic polymorphism on endothelial nitric oxide synthase affects endothelial activation and inflammatory response during the acute phase of myocardial infarction. | OBJECTIVES: This study sought to evaluate the effect of genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS); on the risk for myocardial infarction (MI); and on the release of /"von Willebrand factor"/ (/"vWF"/), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of MI and one year after the event. BACKGROUND: Genetic polymorphism G894T on eNOS has been associated with increased cardiovascular risk. However, its role during the acute phase of MI is unknown. METHODS: The study population consisted of 228 patients with a first event of premature MI and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year. RESULTS: The risk for MI in 894TT was 1.992 (95% confidence interval [CI], 1.131 to 3.485), p < 0.05 versus GG+/"GT"/; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% CI, 1.106 to 3.651), p < 0.05 versus /"GT"/. During the acute phase, /"vWF"/ was higher in /"GT"/+TT (121.02 +/- 5.47%) versus GG (84.6 +/- 7.1%, p < 0.01), an effect persisting after one year (90.4 +/- 3.8 vs. 73.1 +/- 4.6%, p < 0.01). During the acute phase, /"GT"/+TT had higher ox-LDL and IL-6 (131.2 +/- 6.4 IU/l and 8.5 +/- 0.7 pg/ml) compared with GG (101.7 +/- 9.64 IU/l and 6.2 +/- 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year. CONCLUSIONS: G894T polymorphism on the eNOS gene increases the risk for premature MI and modifies the response of vascular endothelium during the acute phase of MI by affecting the release of /"vWF"/, IL-6, and oxidative stress status, an effect diminished one year after the event. | [
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16168956 | Functional polymorphisms of HSPA5: possible association with bipolar disorder. | Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder. | Functional polymorphisms of /"HSPA5"/: possible association with bipolar disorder. | Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of /"HSPA5"/ (/"GRP78"///"BiP"/) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed /"schizophrenia"/ samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in /"schizophrenia"/. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of /"HSPA5"/ may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder. | [
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16168956 | Functional polymorphisms of HSPA5: possible association with bipolar disorder. | Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder. | Functional polymorphisms of /"HSPA5"/: possible association with /"bipolar disorder"/. | Altered endoplasmic reticulum stress (ER) response signaling is suggested in /"bipolar disorder"/. Previously, we preliminarily reported the genetic association of /"HSPA5"/ (/"GRP78"///"BiP"/) with /"bipolar disorder"/. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of /"bipolar disorder"/ but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of /"HSPA5"/ may affect the interindividual variability of ER stress response and may confer a genetic risk factor for /"bipolar disorder"/. | [
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16168956 | Functional polymorphisms of HSPA5: possible association with bipolar disorder. | Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder. | Functional polymorphisms of /"HSPA5"/: possible association with bipolar disorder. | Altered /"endoplasmic reticulum stress"/ (/"ER"/) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of /"HSPA5"/ (/"GRP78"///"BiP"/) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of /"HSPA5"/ may affect the interindividual variability of /"ER"/ stress response and may confer a genetic risk factor for bipolar disorder. | [
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16168956 | Functional polymorphisms of HSPA5: possible association with bipolar disorder. | Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder. | Functional polymorphisms of /"HSPA5"/: possible association with bipolar disorder. | Altered /"endoplasmic reticulum stress"/ (/"ER"/) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of /"HSPA5"/ (/"GRP78"///"BiP"/) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of /"HSPA5"/ may affect the interindividual variability of /"ER"/ stress response and may confer a genetic risk factor for bipolar disorder. | [
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16181776 | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in schizophrenia. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, PLA2G4A and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of schizophrenic patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with schizophrenia (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in schizophrenia and its combination with the CLDN5 gene may increase further the risk for the illness. | A study of the combined effect of the /"CLDN5"/ locus and the genes for the phospholipid metabolism pathway in /"schizophrenia"/. | The present study attempts to test the combined effect of the /"CLDN5"/ gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, PLA2G4A and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of /"schizophrenic"/ patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with /"schizophrenia"/ (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the /"CLDN5"/ gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in /"schizophrenia"/ and its combination with the /"CLDN5"/ gene may increase further the risk for the illness. | [
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16181776 | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in schizophrenia. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, PLA2G4A and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of schizophrenic patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with schizophrenia (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in schizophrenia and its combination with the CLDN5 gene may increase further the risk for the illness. | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in /"schizophrenia"/. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, PLA2G4A and /"PLA2G4C"/. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of /"schizophrenic"/ patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with /"schizophrenia"/ (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in /"schizophrenia"/ and its combination with the CLDN5 gene may increase further the risk for the illness. | [
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16181776 | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in schizophrenia. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, PLA2G4A and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of schizophrenic patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with schizophrenia (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in schizophrenia and its combination with the CLDN5 gene may increase further the risk for the illness. | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in /"schizophrenia"/. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including /"PTGS1"/, PTGS2, PLA2G4A and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of /"schizophrenic"/ patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with /"schizophrenia"/ (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in /"schizophrenia"/ and its combination with the CLDN5 gene may increase further the risk for the illness. | [
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16181776 | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in schizophrenia. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, PLA2G4A and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of schizophrenic patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with schizophrenia (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in schizophrenia and its combination with the CLDN5 gene may increase further the risk for the illness. | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in /"schizophrenia"/. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, /"PTGS2"/, PLA2G4A and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of /"schizophrenic"/ patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with /"schizophrenia"/ (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in /"schizophrenia"/ and its combination with the CLDN5 gene may increase further the risk for the illness. | [
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16181776 | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in schizophrenia. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, PLA2G4A and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of schizophrenic patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the PLA2G4A gene was associated with schizophrenia (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the PLA2G4A locus may be involved in schizophrenia and its combination with the CLDN5 gene may increase further the risk for the illness. | A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in /"schizophrenia"/. | The present study attempts to test the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, /"PLA2G4A"/ and PLA2G4C. We detected five single nucleotide polymorphisms (SNPs) present in these genes among 131 British family trios of /"schizophrenic"/ patients. The transmission disequilibrium test (TDT) showed that BanI-SNP located in the 5'-flanking region of the /"PLA2G4A"/ gene was associated with /"schizophrenia"/ (chi(2) = 5.16, P = 0.023) although the others failed to show such allelic associations. The global P-value was 0.150 for 1000 permutations with the TDT analysis. The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the /"PLA2G4A"/ gene (chi(2) = 10.17, df = 2, P = 0.006). The present results suggest that the /"PLA2G4A"/ locus may be involved in /"schizophrenia"/ and its combination with the CLDN5 gene may increase further the risk for the illness. | [
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16182378 | CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis. | Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS. | CCR5Delta32 polymorphism effects on /"CCR5"/ expression, patterns of immunopathology and disease course in /"multiple sclerosis"/. | Four distinct patterns of tissue injury have been described in /"multiple sclerosis"/ (/"MS"/) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and /"CCR5"/. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of /"CCR5"/ expressing cells is increased in late active versus early active regions. In contrast, CCR1 and /"CCR5"/ cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support /"MS"/ pathological heterogeneity. A deletion in /"CCR5"/ (/"CCR5*Delta32"/), which encodes a truncated, non-functional protein, has been associated with late onset of /"MS"/ and a favorable prognosis. We studied the association of /"CCR5*Delta32"/ with the course and severity of /"MS"/ in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the /"MS"/ Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the /"CCR5"/*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the /"CCR5*Delta32"/ mutation was not associated with patterns of immunopathology in /"MS"/. Despite similar numbers of T-lymphocytes, there were no /"CCR5"/+ T-cells nor was /"CCR5"/ expressed in the CNS of a homozygous /"CCR5"/*Delta32 /"MS"/ patient, and heterozygous patients had reduced /"CCR5"/ expression compared to wild type patients. /"CCR5*Delta32"/ has a dose effect on /"CCR5"/ expression in the CNS, but is neither necessary for development of /"MS"/, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in /"MS"/. We did not find an association between /"CCR5*Delta32"/ mutation and disease severity and age of onset in /"MS"/. | [
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16182378 | CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis. | Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS. | CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in /"multiple sclerosis"/. | Four distinct patterns of tissue injury have been described in /"multiple sclerosis"/ (/"MS"/) lesions. Infiltrating monocytes in lesions of all patterns co-express /"CCR1"/ and CCR5. However, in pattern II lesions, the number of /"CCR1"/ cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, /"CCR1"/ and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support /"MS"/ pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of /"MS"/ and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of /"MS"/ in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the /"MS"/ Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in /"MS"/. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 /"MS"/ patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of /"MS"/, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in /"MS"/. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in /"MS"/. | [
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16182378 | CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis. | Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS. | CCR5Delta32 polymorphism effects on /"CCR5"/ expression, patterns of immunopathology and /"disease course"/ in multiple sclerosis. | Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and /"CCR5"/. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of /"CCR5"/ expressing cells is increased in late active versus early active regions. In contrast, CCR1 and /"CCR5"/ cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in /"CCR5"/ (/"CCR5*Delta32"/), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of /"CCR5*Delta32"/ with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the /"CCR5"/*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or /"disease course"/ (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the /"CCR5*Delta32"/ mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no /"CCR5"/+ T-cells nor was /"CCR5"/ expressed in the CNS of a homozygous /"CCR5"/*Delta32 MS patient, and heterozygous patients had reduced /"CCR5"/ expression compared to wild type patients. /"CCR5*Delta32"/ has a dose effect on /"CCR5"/ expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between /"CCR5*Delta32"/ mutation and disease severity and age of onset in MS. | [
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16182378 | CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis. | Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS. | CCR5Delta32 polymorphism effects on /"CCR5"/ expression, patterns of immunopathology and disease course in multiple sclerosis. | Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and /"CCR5"/. However, in /"pattern II lesions"/, the number of CCR1 cells is decreased, while the number of /"CCR5"/ expressing cells is increased in late active versus early active regions. In contrast, CCR1 and /"CCR5"/ cells were equal in all regions of /"pattern III lesions"/. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in /"CCR5"/ (/"CCR5*Delta32"/), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of /"CCR5*Delta32"/ with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the /"CCR5"/*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the /"CCR5*Delta32"/ mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no /"CCR5"/+ T-cells nor was /"CCR5"/ expressed in the CNS of a homozygous /"CCR5"/*Delta32 MS patient, and heterozygous patients had reduced /"CCR5"/ expression compared to wild type patients. /"CCR5*Delta32"/ has a dose effect on /"CCR5"/ expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between /"CCR5*Delta32"/ mutation and disease severity and age of onset in MS. | [
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16183801 | Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients. | MECP2 mutations are identifiable in approximately 80% of classic Rett syndrome (RTT), but less frequently in atypical RTT. We recruited 110 patients who fulfilled the diagnostic criteria for Rett syndrome and were referred to Cardiff for molecular analysis, but in whom an MECP2 mutation was not identifiable. Dosage analysis of MECP2 was carried out using multiplex ligation dependent probe amplification or quantitative fluorescent PCR. Large deletions were identified in 37.8% (14/37) of classic and 7.5% (4/53) of atypical RTT patients. Most large deletions contained a breakpoint in the deletion prone region of exon 4. The clinical phenotype was ascertained in all 18 of the deleted cases and in four further cases with large deletions identified in Goettingen. Five patients with large deletions had additional congenital anomalies, which was significantly more than in RTT patients with other MECP2 mutations (2/193; p<0.0001). Quantitative analysis should be included in molecular diagnostic strategies in both classic and atypical RTT. | Gross rearrangements of the /"MECP2"/ gene are found in both classical and atypical /"Rett syndrome"/ patients. | /"MECP2"/ mutations are identifiable in approximately 80% of classic /"Rett syndrome"/ (/"RTT"/), but less frequently in atypical /"RTT"/. We recruited 110 patients who fulfilled the diagnostic criteria for /"Rett syndrome"/ and were referred to Cardiff for molecular analysis, but in whom an /"MECP2"/ mutation was not identifiable. Dosage analysis of /"MECP2"/ was carried out using multiplex ligation dependent probe amplification or quantitative fluorescent PCR. Large deletions were identified in 37.8% (14/37) of classic and 7.5% (4/53) of atypical /"RTT"/ patients. Most large deletions contained a breakpoint in the deletion prone region of exon 4. The clinical phenotype was ascertained in all 18 of the deleted cases and in four further cases with large deletions identified in Goettingen. Five patients with large deletions had additional congenital anomalies, which was significantly more than in /"RTT"/ patients with other /"MECP2"/ mutations (2/193; p<0.0001). Quantitative analysis should be included in molecular diagnostic strategies in both classic and atypical /"RTT"/. | [
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16183801 | Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients. | MECP2 mutations are identifiable in approximately 80% of classic Rett syndrome (RTT), but less frequently in atypical RTT. We recruited 110 patients who fulfilled the diagnostic criteria for Rett syndrome and were referred to Cardiff for molecular analysis, but in whom an MECP2 mutation was not identifiable. Dosage analysis of MECP2 was carried out using multiplex ligation dependent probe amplification or quantitative fluorescent PCR. Large deletions were identified in 37.8% (14/37) of classic and 7.5% (4/53) of atypical RTT patients. Most large deletions contained a breakpoint in the deletion prone region of exon 4. The clinical phenotype was ascertained in all 18 of the deleted cases and in four further cases with large deletions identified in Goettingen. Five patients with large deletions had additional congenital anomalies, which was significantly more than in RTT patients with other MECP2 mutations (2/193; p<0.0001). Quantitative analysis should be included in molecular diagnostic strategies in both classic and atypical RTT. | Gross rearrangements of the /"MECP2"/ gene are found in both classical and atypical Rett syndrome patients. | /"MECP2"/ mutations are identifiable in approximately 80% of classic Rett syndrome (RTT), but less frequently in atypical RTT. We recruited 110 patients who fulfilled the diagnostic criteria for Rett syndrome and were referred to Cardiff for molecular analysis, but in whom an /"MECP2"/ mutation was not identifiable. Dosage analysis of /"MECP2"/ was carried out using multiplex ligation dependent probe amplification or quantitative fluorescent PCR. Large deletions were identified in 37.8% (14/37) of classic and 7.5% (4/53) of atypical RTT patients. Most large deletions contained a breakpoint in the deletion prone region of exon 4. The clinical phenotype was ascertained in all 18 of the deleted cases and in four further cases with large deletions identified in Goettingen. Five patients with large deletions had additional /"congenital anomalies"/, which was significantly more than in RTT patients with other /"MECP2"/ mutations (2/193; p<0.0001). Quantitative analysis should be included in molecular diagnostic strategies in both classic and atypical RTT. | [
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16187919 | Total iodide organification defect: clinical and molecular characterization of an Italian family. | Thyroid peroxidase (TPO) deficiency is frequently involved in total iodide organification defects (TIOD). According to the recessive mode of inheritance, mutations are found in homozygous or in compound heterozygous states. However, a single heterozygous TPO mutation is reported in a high percentage (approximately 20%) of patients with typical TIOD phenotype. In the present study, the genetic and clinical evaluation of a TIOD family is reported. The propositus is an Italian girl with congenital hypothyroidism and positive perchlorate discharge test. Two TPO frameshift mutations were documented: a C deletion at 477 in exon 5, and a GGCC duplication at 1277 in exon 8. Unaffected family members, heterozygous for one of the two TPO mutations, were also studied in order to evaluate in vivo the functional activity of a single TPO allele. They have been found to have normal thyroid morphology and function with normal perchlorate test. In conclusion, the present study reports the clinical and molecular investigations in an Italian TIOD family. The results show that the TIOD phenotype in the propositus is associated to a compound heterozygous pattern, while a single TPO mutation does not significantly affect in vivo the efficiency of iodide organification. Therefore, extensive analyses of TPO gene and 2p25 locus are needed in the frequent TIOD cases in whom conventional investigations disclosed only one mutant allele. | Total iodide organification defect: clinical and molecular characterization of an Italian family. | /"Thyroid peroxidase"/ (/"TPO"/) deficiency is frequently involved in total iodide organification defects (TIOD). According to the recessive mode of inheritance, mutations are found in homozygous or in compound heterozygous states. However, a single heterozygous /"TPO"/ mutation is reported in a high percentage (approximately 20%) of patients with typical TIOD phenotype. In the present study, the genetic and clinical evaluation of a TIOD family is reported. The propositus is an Italian girl with /"congenital hypothyroidism"/ and positive perchlorate discharge test. Two /"TPO"/ frameshift mutations were documented: a C deletion at 477 in exon 5, and a GGCC duplication at 1277 in exon 8. Unaffected family members, heterozygous for one of the two /"TPO"/ mutations, were also studied in order to evaluate in vivo the functional activity of a single /"TPO"/ allele. They have been found to have normal thyroid morphology and function with normal perchlorate test. In conclusion, the present study reports the clinical and molecular investigations in an Italian TIOD family. The results show that the TIOD phenotype in the propositus is associated to a compound heterozygous pattern, while a single /"TPO"/ mutation does not significantly affect in vivo the efficiency of iodide organification. Therefore, extensive analyses of /"TPO"/ gene and 2p25 locus are needed in the frequent TIOD cases in whom conventional investigations disclosed only one mutant allele. | [
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} | Yes |
16187919 | Total iodide organification defect: clinical and molecular characterization of an Italian family. | Thyroid peroxidase (TPO) deficiency is frequently involved in total iodide organification defects (TIOD). According to the recessive mode of inheritance, mutations are found in homozygous or in compound heterozygous states. However, a single heterozygous TPO mutation is reported in a high percentage (approximately 20%) of patients with typical TIOD phenotype. In the present study, the genetic and clinical evaluation of a TIOD family is reported. The propositus is an Italian girl with congenital hypothyroidism and positive perchlorate discharge test. Two TPO frameshift mutations were documented: a C deletion at 477 in exon 5, and a GGCC duplication at 1277 in exon 8. Unaffected family members, heterozygous for one of the two TPO mutations, were also studied in order to evaluate in vivo the functional activity of a single TPO allele. They have been found to have normal thyroid morphology and function with normal perchlorate test. In conclusion, the present study reports the clinical and molecular investigations in an Italian TIOD family. The results show that the TIOD phenotype in the propositus is associated to a compound heterozygous pattern, while a single TPO mutation does not significantly affect in vivo the efficiency of iodide organification. Therefore, extensive analyses of TPO gene and 2p25 locus are needed in the frequent TIOD cases in whom conventional investigations disclosed only one mutant allele. | Total iodide organification defect: clinical and molecular characterization of an Italian family. | /"Thyroid peroxidase"/ (/"TPO"/) deficiency is frequently involved in /"total iodide organification defects"/ (/"TIOD"/). According to the recessive mode of inheritance, mutations are found in homozygous or in compound heterozygous states. However, a single heterozygous /"TPO"/ mutation is reported in a high percentage (approximately 20%) of patients with typical /"TIOD"/ phenotype. In the present study, the genetic and clinical evaluation of a /"TIOD"/ family is reported. The propositus is an Italian girl with congenital hypothyroidism and positive perchlorate discharge test. Two /"TPO"/ frameshift mutations were documented: a C deletion at 477 in exon 5, and a GGCC duplication at 1277 in exon 8. Unaffected family members, heterozygous for one of the two /"TPO"/ mutations, were also studied in order to evaluate in vivo the functional activity of a single /"TPO"/ allele. They have been found to have normal thyroid morphology and function with normal perchlorate test. In conclusion, the present study reports the clinical and molecular investigations in an Italian /"TIOD"/ family. The results show that the /"TIOD"/ phenotype in the propositus is associated to a compound heterozygous pattern, while a single /"TPO"/ mutation does not significantly affect in vivo the efficiency of iodide organification. Therefore, extensive analyses of /"TPO"/ gene and 2p25 locus are needed in the frequent /"TIOD"/ cases in whom conventional investigations disclosed only one mutant allele. | [
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16189508 | Extreme population differences across Neuregulin 1 gene, with implications for association studies. | Neuregulin 1 (NRG1) is one of the most exciting candidate genes for schizophrenia in recent years since its first association with the disease in an Icelandic population. Since then, many association studies have analysed allele and haplotype frequencies in distinct populations yielding varying results: some have replicated the association, although with different alleles or haplotypes being associated, whereas others have failed to replicate the association. These contradictory results might be attributed to population differences in allele and haplotype frequencies. In order to approach this issue, we have typed 13 SNPs across this large 1.4 Mb gene, including two of the SNPs originally found associated with schizophrenia in the Icelandic population, the objective being to discover if the underlying cause of the association discrepancies to date may be due to population-specific genetic variation. The analyses have been performed in a total of 1088 individuals from 39 populations, covering most of the genetic diversity in the human species. Most of the SNPs analysed displayed differing frequencies according to geographical region. These allele differences are especially relevant in two SNPs located in a large intron of the gene, as shown by the extreme F(ST) values, which reveal genetic stratification correlated to broad continental areas. This finding may be indicative of the influence of some local selective forces on this gene. Furthermore, haplotype analysis reveals a clear clustering according to geographical areas. In summary, our findings suggest that NRG1 presents extreme population differences in allele and haplotype frequencies. We have given recommendations for taking this into account in future association studies since this diversity could give rise to erroneous results. | Extreme population differences across /"Neuregulin 1"/ gene, with implications for association studies. | /"Neuregulin 1"/ (/"NRG1"/) is one of the most exciting candidate genes for /"schizophrenia"/ in recent years since its first association with the disease in an Icelandic population. Since then, many association studies have analysed allele and haplotype frequencies in distinct populations yielding varying results: some have replicated the association, although with different alleles or haplotypes being associated, whereas others have failed to replicate the association. These contradictory results might be attributed to population differences in allele and haplotype frequencies. In order to approach this issue, we have typed 13 SNPs across this large 1.4 Mb gene, including two of the SNPs originally found associated with /"schizophrenia"/ in the Icelandic population, the objective being to discover if the underlying cause of the association discrepancies to date may be due to population-specific genetic variation. The analyses have been performed in a total of 1088 individuals from 39 populations, covering most of the genetic diversity in the human species. Most of the SNPs analysed displayed differing frequencies according to geographical region. These allele differences are especially relevant in two SNPs located in a large intron of the gene, as shown by the extreme F(ST) values, which reveal genetic stratification correlated to broad continental areas. This finding may be indicative of the influence of some local selective forces on this gene. Furthermore, haplotype analysis reveals a clear clustering according to geographical areas. In summary, our findings suggest that /"NRG1"/ presents extreme population differences in allele and haplotype frequencies. We have given recommendations for taking this into account in future association studies since this diversity could give rise to erroneous results. | [
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16194568 | Differential effects of vigabatrin and zonisamide on the neuropeptide Y system in the hippocampus of seizure prone gerbil. | Changed neuropeptide Y (NPY) system in the hippocampus has been reported in various experimental epileptic models. However, there have been little data concerning the alteration in the NPY system in the epileptic hippocampus following treatment of anti-epileptic drugs (AEDs). In the present study, therefore, we performed analyses of effects of vigabatrin (VGB) and zonisamide (ZNS) treatment on the NPY system in the hippocampus of the seizure sensitive (SS) gerbils. In SS gerbil, NPY immunoreactivity in the hippocampus was lower than that in seizure resistant gerbil. Following VGB treatment, the number of NPY immunoreactive neurons and NPY mRNA expression were increased in the hilus and the hippocampus proper. In contrast, ZNS treatment markedly elevated only the density of NPY immunoreactive fibers in the dentate gyrus, not in the hippocampus proper, as compared with saline-treated animals. These patterns were observed in the dose-dependent manners. These findings suggest that AEDs treatments may distinctly affect the NPY system in the SS gerbil hippocampus. | Differential effects of vigabatrin and zonisamide on the /"neuropeptide Y"/ system in the hippocampus of /"seizure"/ prone gerbil. | Changed /"neuropeptide Y"/ (/"NPY"/) system in the hippocampus has been reported in various experimental epileptic models. However, there have been little data concerning the alteration in the /"NPY"/ system in the epileptic hippocampus following treatment of anti-epileptic drugs (AEDs). In the present study, therefore, we performed analyses of effects of vigabatrin (VGB) and zonisamide (ZNS) treatment on the /"NPY"/ system in the hippocampus of the /"seizure sensitive"/ (/"SS"/) gerbils. In /"SS"/ gerbil, /"NPY"/ immunoreactivity in the hippocampus was lower than that in /"seizure"/ resistant gerbil. Following VGB treatment, the number of /"NPY"/ immunoreactive neurons and /"NPY"/ mRNA expression were increased in the hilus and the hippocampus proper. In contrast, ZNS treatment markedly elevated only the density of /"NPY"/ immunoreactive fibers in the dentate gyrus, not in the hippocampus proper, as compared with saline-treated animals. These patterns were observed in the dose-dependent manners. These findings suggest that AEDs treatments may distinctly affect the /"NPY"/ system in the /"SS"/ gerbil hippocampus. | [
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16194568 | Differential effects of vigabatrin and zonisamide on the neuropeptide Y system in the hippocampus of seizure prone gerbil. | Changed neuropeptide Y (NPY) system in the hippocampus has been reported in various experimental epileptic models. However, there have been little data concerning the alteration in the NPY system in the epileptic hippocampus following treatment of anti-epileptic drugs (AEDs). In the present study, therefore, we performed analyses of effects of vigabatrin (VGB) and zonisamide (ZNS) treatment on the NPY system in the hippocampus of the seizure sensitive (SS) gerbils. In SS gerbil, NPY immunoreactivity in the hippocampus was lower than that in seizure resistant gerbil. Following VGB treatment, the number of NPY immunoreactive neurons and NPY mRNA expression were increased in the hilus and the hippocampus proper. In contrast, ZNS treatment markedly elevated only the density of NPY immunoreactive fibers in the dentate gyrus, not in the hippocampus proper, as compared with saline-treated animals. These patterns were observed in the dose-dependent manners. These findings suggest that AEDs treatments may distinctly affect the NPY system in the SS gerbil hippocampus. | Differential effects of vigabatrin and zonisamide on the /"neuropeptide Y"/ system in the hippocampus of seizure prone gerbil. | Changed /"neuropeptide Y"/ (/"NPY"/) system in the hippocampus has been reported in various experimental /"epileptic"/ models. However, there have been little data concerning the alteration in the /"NPY"/ system in the /"epileptic"/ hippocampus following treatment of /"anti-epileptic drugs"/ (/"AEDs"/). In the present study, therefore, we performed analyses of effects of vigabatrin (VGB) and zonisamide (ZNS) treatment on the /"NPY"/ system in the hippocampus of the seizure sensitive (SS) gerbils. In SS gerbil, /"NPY"/ immunoreactivity in the hippocampus was lower than that in seizure resistant gerbil. Following VGB treatment, the number of /"NPY"/ immunoreactive neurons and /"NPY"/ mRNA expression were increased in the hilus and the hippocampus proper. In contrast, ZNS treatment markedly elevated only the density of /"NPY"/ immunoreactive fibers in the dentate gyrus, not in the hippocampus proper, as compared with saline-treated animals. These patterns were observed in the dose-dependent manners. These findings suggest that /"AEDs"/ treatments may distinctly affect the /"NPY"/ system in the SS gerbil hippocampus. | [
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16211375 | Polymorphisms in the gene encoding angiotensin I converting enzyme 2 and diabetic nephropathy. | AIMS/HYPOTHESIS: Substantial evidence exists for the involvement of the renin-angiotensin system (RAS) in diabetic nephropathy. Angiotensin I converting enzyme 2 (ACE2), a new component of the RAS, has been implicated in kidney disease, hypertension and cardiac function. Based on this, the aim of the present study was to evaluate whether variations in ACE2 are associated with diabetic nephropathy. MATERIALS AND METHODS: We used a cross-sectional, case-control study design to investigate 823 Finnish type 1 diabetic patients (365 with and 458 without nephropathy). Five single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan technology. Haplotypes were estimated using PHASE software, and haplotype frequency differences were analysed using a chi(2)-test-based tool. RESULTS: None of the ACE2 polymorphisms was associated with diabetic nephropathy, and this finding was supported by the haplotype analysis. The ACE2 polymorphisms were not associated with blood pressure, BMI or HbA(1)c. CONCLUSIONS/INTERPRETATION: In Finnish type 1 diabetic patients, ACE2 polymorphisms are not associated with diabetic nephropathy or any studied risk factor for this complication. Further studies are necessary to assess a minor effect of ACE2. | Polymorphisms in the gene encoding /"angiotensin I converting enzyme 2"/ and /"diabetic nephropathy"/. | AIMS/HYPOTHESIS: Substantial evidence exists for the involvement of the renin-angiotensin system (RAS) in /"diabetic nephropathy"/. /"Angiotensin I converting enzyme 2"/ (/"ACE2"/), a new component of the RAS, has been implicated in kidney disease, hypertension and cardiac function. Based on this, the aim of the present study was to evaluate whether variations in /"ACE2"/ are associated with /"diabetic nephropathy"/. MATERIALS AND METHODS: We used a cross-sectional, case-control study design to investigate 823 Finnish type 1 diabetic patients (365 with and 458 without nephropathy). Five single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan technology. Haplotypes were estimated using PHASE software, and haplotype frequency differences were analysed using a chi(2)-test-based tool. RESULTS: None of the /"ACE2"/ polymorphisms was associated with /"diabetic nephropathy"/, and this finding was supported by the haplotype analysis. The /"ACE2"/ polymorphisms were not associated with blood pressure, BMI or HbA(1)c. CONCLUSIONS/INTERPRETATION: In Finnish type 1 diabetic patients, /"ACE2"/ polymorphisms are not associated with /"diabetic nephropathy"/ or any studied risk factor for this complication. Further studies are necessary to assess a minor effect of /"ACE2"/. | [
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16211375 | Polymorphisms in the gene encoding angiotensin I converting enzyme 2 and diabetic nephropathy. | AIMS/HYPOTHESIS: Substantial evidence exists for the involvement of the renin-angiotensin system (RAS) in diabetic nephropathy. Angiotensin I converting enzyme 2 (ACE2), a new component of the RAS, has been implicated in kidney disease, hypertension and cardiac function. Based on this, the aim of the present study was to evaluate whether variations in ACE2 are associated with diabetic nephropathy. MATERIALS AND METHODS: We used a cross-sectional, case-control study design to investigate 823 Finnish type 1 diabetic patients (365 with and 458 without nephropathy). Five single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan technology. Haplotypes were estimated using PHASE software, and haplotype frequency differences were analysed using a chi(2)-test-based tool. RESULTS: None of the ACE2 polymorphisms was associated with diabetic nephropathy, and this finding was supported by the haplotype analysis. The ACE2 polymorphisms were not associated with blood pressure, BMI or HbA(1)c. CONCLUSIONS/INTERPRETATION: In Finnish type 1 diabetic patients, ACE2 polymorphisms are not associated with diabetic nephropathy or any studied risk factor for this complication. Further studies are necessary to assess a minor effect of ACE2. | Polymorphisms in the gene encoding /"angiotensin I converting enzyme 2"/ and diabetic nephropathy. | AIMS/HYPOTHESIS: Substantial evidence exists for the involvement of the renin-angiotensin system (RAS) in diabetic nephropathy. /"Angiotensin I converting enzyme 2"/ (/"ACE2"/), a new component of the RAS, has been implicated in /"kidney disease"/, hypertension and cardiac function. Based on this, the aim of the present study was to evaluate whether variations in /"ACE2"/ are associated with diabetic nephropathy. MATERIALS AND METHODS: We used a cross-sectional, case-control study design to investigate 823 Finnish type 1 diabetic patients (365 with and 458 without /"nephropathy"/). Five single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan technology. Haplotypes were estimated using PHASE software, and haplotype frequency differences were analysed using a chi(2)-test-based tool. RESULTS: None of the /"ACE2"/ polymorphisms was associated with diabetic nephropathy, and this finding was supported by the haplotype analysis. The /"ACE2"/ polymorphisms were not associated with blood pressure, BMI or HbA(1)c. CONCLUSIONS/INTERPRETATION: In Finnish type 1 diabetic patients, /"ACE2"/ polymorphisms are not associated with diabetic nephropathy or any studied risk factor for this complication. Further studies are necessary to assess a minor effect of /"ACE2"/. | [
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16219118 | Neuregulin 1 (NRG1 ) and schizophrenia: analysis of a US family sample and the evidence in the balance. | BACKGROUND: Individual genome-wide linkage scans and meta-analyses support that one or more susceptibility genes for schizophrenia are located in chromosome 8p. A gene from this region, neuregulin 1 (NRG1 ), known to be involved with glutamatergic function, has been found to be associated in some studied samples. METHOD: We have examined a new combined schizophrenia sample with 136 schizophrenia families largely of European ancestry (EA) and 646 subjects with DNA. We genotyped 14 single nucleotide polymorphisms (SNPs) in NRG1 including those reported to comprise schizophrenia-associated haplotypes in Icelandic, Scottish, Irish, and Chinese Han populations. RESULTS: We found no evidence of association at a single-marker or a haplotypic level. We review methodological aspects of previous studies to enable us to put our findings into context. CONCLUSIONS: Our failure to find an association between NRG1 and schizophrenia might reflect different linkage disequilibrium (LD) patterns found in different populations, disease allelic heterogeneity, clinical heterogeneity of schizophrenia, or inadequate statistical power deriving from moderate sample size. NRG1, if a true gene for schizophrenia, accounts for a small fraction of the disease in most populations. The confirmation of NRG1 as a schizophrenia susceptibility gene will require studies with a comprehensive set of markers and in larger samples. The possibility remains that reports of NRG1 association might reflect false positives. | /"Neuregulin 1"/ (/"NRG1"/ ) and /"schizophrenia"/: analysis of a US family sample and the evidence in the balance. | BACKGROUND: Individual genome-wide linkage scans and meta-analyses support that one or more susceptibility genes for /"schizophrenia"/ are located in chromosome 8p. A gene from this region, /"neuregulin 1"/ (/"NRG1"/ ), known to be involved with glutamatergic function, has been found to be associated in some studied samples. METHOD: We have examined a new combined /"schizophrenia"/ sample with 136 /"schizophrenia"/ families largely of European ancestry (EA) and 646 subjects with DNA. We genotyped 14 single nucleotide polymorphisms (SNPs) in /"NRG1"/ including those reported to comprise /"schizophrenia"/-associated haplotypes in Icelandic, Scottish, Irish, and Chinese Han populations. RESULTS: We found no evidence of association at a single-marker or a haplotypic level. We review methodological aspects of previous studies to enable us to put our findings into context. CONCLUSIONS: Our failure to find an association between /"NRG1"/ and /"schizophrenia"/ might reflect different linkage disequilibrium (LD) patterns found in different populations, disease allelic heterogeneity, clinical heterogeneity of /"schizophrenia"/, or inadequate statistical power deriving from moderate sample size. /"NRG1"/, if a true gene for /"schizophrenia"/, accounts for a small fraction of the disease in most populations. The confirmation of /"NRG1"/ as a /"schizophrenia"/ susceptibility gene will require studies with a comprehensive set of markers and in larger samples. The possibility remains that reports of /"NRG1"/ association might reflect false positives. | [
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} | Yes |
16222672 | Letter to the editor: Novel GJA1 mutation in oculodentodigital dysplasia. | Letter to the editor: Novel /"GJA1"/ mutation in /"oculodentodigital dysplasia"/. | [
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"text_name": "oculodentodigital dysplasia"
} | Yes |
||
16226919 | Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. | The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no detectable 11-cis-retinal, but markedly elevated retinyl esters. Subretinal AAV-RPE65 treatment resulted in detectable 11-cis-retinal expression, limited to treated areas. RPE65 protein expression was limited to retinal pigment epithelium of treated areas. Subretinal AAV-RPE65 vector is well tolerated and does not elicit high antibody levels to the vector or the protein in ocular fluids or serum. In long-term studies, wild-type cDNA is expressed only in target cells. Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by RPE65 mutations. | Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of /"childhood blindness"/. | The short- and long-term effects of gene therapy using AAV-mediated /"RPE65"/ transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine /"RPE65"/ cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no detectable 11-cis-retinal, but markedly elevated retinyl esters. Subretinal AAV-/"RPE65"/ treatment resulted in detectable 11-cis-retinal expression, limited to treated areas. /"RPE65"/ protein expression was limited to retinal pigment epithelium of treated areas. Subretinal AAV-/"RPE65"/ vector is well tolerated and does not elicit high antibody levels to the vector or the protein in ocular fluids or serum. In long-term studies, wild-type cDNA is expressed only in target cells. Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by /"RPE65"/ mutations. | [
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} | Yes |
16226919 | Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. | The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no detectable 11-cis-retinal, but markedly elevated retinyl esters. Subretinal AAV-RPE65 treatment resulted in detectable 11-cis-retinal expression, limited to treated areas. RPE65 protein expression was limited to retinal pigment epithelium of treated areas. Subretinal AAV-RPE65 vector is well tolerated and does not elicit high antibody levels to the vector or the protein in ocular fluids or serum. In long-term studies, wild-type cDNA is expressed only in target cells. Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by RPE65 mutations. | Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. | The short- and long-term effects of gene therapy using AAV-mediated /"RPE65"/ transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by /"RPE65 deficiency"/. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine /"RPE65"/ cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no detectable 11-cis-retinal, but markedly elevated retinyl esters. Subretinal AAV-/"RPE65"/ treatment resulted in detectable 11-cis-retinal expression, limited to treated areas. /"RPE65"/ protein expression was limited to retinal pigment epithelium of treated areas. Subretinal AAV-/"RPE65"/ vector is well tolerated and does not elicit high antibody levels to the vector or the protein in ocular fluids or serum. In long-term studies, wild-type cDNA is expressed only in target cells. Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by /"RPE65"/ mutations. | [
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16230376 | Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. | Serum levels of amphiregulin and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum amphiregulin or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). Amphiregulin or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC. | Increases of /"amphiregulin"/ and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced /"non-small cell lung cancers"/. | Serum levels of /"amphiregulin"/ and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in /"non-small cell lung cancer"/ (/"NSCLC"/) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for /"amphiregulin"/ in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated /"NSCLC"/ patients whose serum /"amphiregulin"/ or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum /"amphiregulin"/ or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among /"NSCLC"/ patients treated with gefitinib (P = 0.034). /"Amphiregulin"/ or TGF-alpha positivity in /"NSCLC"/ tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of /"amphiregulin"/ and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced /"NSCLC"/. | [
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16230376 | Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. | Serum levels of amphiregulin and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum amphiregulin or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). Amphiregulin or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC. | Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced /"non-small cell lung cancers"/. | Serum levels of amphiregulin and transforming growth factor-alpha (/"TGF-alpha"/), which were identified previously to be expressed at high levels in /"non-small cell lung cancer"/ (/"NSCLC"/) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for /"TGF-alpha"/ responded poorly to gefitinib, whereas 18 of the 35 patients with negative /"TGF-alpha"/ levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated /"NSCLC"/ patients whose serum amphiregulin or /"TGF-alpha"/ was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or /"TGF-alpha"/ concentrations were negative. Multivariate analysis showed an independent association between positivity for /"TGF-alpha"/ and shorter survival times among /"NSCLC"/ patients treated with gefitinib (P = 0.034). Amphiregulin or /"TGF-alpha"/ positivity in /"NSCLC"/ tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and /"TGF-alpha"/ in serum can be an important predictor of the resistance to gefitinib among patients with advanced /"NSCLC"/. | [
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16230376 | Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. | Serum levels of amphiregulin and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum amphiregulin or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). Amphiregulin or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC. | Increases of /"amphiregulin"/ and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. | Serum levels of /"amphiregulin"/ and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for /"amphiregulin"/ in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or /"stable disease"/ (/"SD"/; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or /"SD"/ groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum /"amphiregulin"/ or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum /"amphiregulin"/ or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). /"Amphiregulin"/ or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of /"amphiregulin"/ and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC. | [
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16230376 | Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. | Serum levels of amphiregulin and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum amphiregulin or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). Amphiregulin or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC. | Increases of /"amphiregulin"/ and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. | Serum levels of /"amphiregulin"/ and transforming growth factor-alpha (TGF-alpha), which were identified previously to be expressed at high levels in non-small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for /"amphiregulin"/ in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or /"stable disease"/ (/"SD"/; P = 0.026). Thirteen of 15 patients who were positive for TGF-alpha responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-alpha levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or /"SD"/ groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum /"amphiregulin"/ or TGF-alpha was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum /"amphiregulin"/ or TGF-alpha concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-alpha and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). /"Amphiregulin"/ or TGF-alpha positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of /"amphiregulin"/ and TGF-alpha in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC. | [
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16230779 | RET polymorphisms and sporadic medullary thyroid carcinoma in a Portuguese population. | The genetic basis of the sporadic form of medullary thyroid carcinoma, derived from "C" cells, is still poorly understood. Somatic mutations of RET proto-oncogene have been reported at a variable frequency ranging from 23% to 69%. The hypothesis that low penetrance factors, such as polymorphisms, might contribute to the phenotype of this neoplasm has been addressed in a few studies conducting to conflicting results. Herein, we studied 100 individuals (50 patients and 50 controls) aiming to compare the frequencies of G691S, L769L, S836S, and S904S RET polymorphisms observed in patients with respect to controls. Furthermore, meta-analysis of published studies including the present results was conducted. To test the contributory role of the above polymorphisms for the development of "C"-cell hyperplasia, we studied a group of 10 individuals selected for having a positive pentagastrin test despite the absence of a RET germline mutation. An over-representation of the G691S polymorphism, particularly in females, was observed in patients with respect to controls, although not reaching the level of significance. Allelic frequencies of the other three polymorphisms were not different in patients and controls. Results obtained in the admittedly small group of individuals with a positive pentagastrin test are unlikely to support a major influence of any polymorphism in the development of "C"-cell hyperplasia. The meta-analysis provided evidence for a significant association of the S691 allele with MTC (odds ratio 1.54, 95% confidence interval 1.12-2.12, p=0.008) and found no significant associations for the other polymorphisms. | /"RET"/ polymorphisms and sporadic /"medullary thyroid carcinoma"/ in a Portuguese population. | The genetic basis of the sporadic form of /"medullary thyroid carcinoma"/, derived from "C" cells, is still poorly understood. Somatic mutations of /"RET"/ proto-oncogene have been reported at a variable frequency ranging from 23% to 69%. The hypothesis that low penetrance factors, such as polymorphisms, might contribute to the phenotype of this neoplasm has been addressed in a few studies conducting to conflicting results. Herein, we studied 100 individuals (50 patients and 50 controls) aiming to compare the frequencies of G691S, L769L, S836S, and S904S /"RET"/ polymorphisms observed in patients with respect to controls. Furthermore, meta-analysis of published studies including the present results was conducted. To test the contributory role of the above polymorphisms for the development of "C"-cell hyperplasia, we studied a group of 10 individuals selected for having a positive pentagastrin test despite the absence of a /"RET"/ germline mutation. An over-representation of the G691S polymorphism, particularly in females, was observed in patients with respect to controls, although not reaching the level of significance. Allelic frequencies of the other three polymorphisms were not different in patients and controls. Results obtained in the admittedly small group of individuals with a positive pentagastrin test are unlikely to support a major influence of any polymorphism in the development of "C"-cell hyperplasia. The meta-analysis provided evidence for a significant association of the S691 allele with MTC (odds ratio 1.54, 95% confidence interval 1.12-2.12, p=0.008) and found no significant associations for the other polymorphisms. | [
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16230779 | RET polymorphisms and sporadic medullary thyroid carcinoma in a Portuguese population. | The genetic basis of the sporadic form of medullary thyroid carcinoma, derived from "C" cells, is still poorly understood. Somatic mutations of RET proto-oncogene have been reported at a variable frequency ranging from 23% to 69%. The hypothesis that low penetrance factors, such as polymorphisms, might contribute to the phenotype of this neoplasm has been addressed in a few studies conducting to conflicting results. Herein, we studied 100 individuals (50 patients and 50 controls) aiming to compare the frequencies of G691S, L769L, S836S, and S904S RET polymorphisms observed in patients with respect to controls. Furthermore, meta-analysis of published studies including the present results was conducted. To test the contributory role of the above polymorphisms for the development of "C"-cell hyperplasia, we studied a group of 10 individuals selected for having a positive pentagastrin test despite the absence of a RET germline mutation. An over-representation of the G691S polymorphism, particularly in females, was observed in patients with respect to controls, although not reaching the level of significance. Allelic frequencies of the other three polymorphisms were not different in patients and controls. Results obtained in the admittedly small group of individuals with a positive pentagastrin test are unlikely to support a major influence of any polymorphism in the development of "C"-cell hyperplasia. The meta-analysis provided evidence for a significant association of the S691 allele with MTC (odds ratio 1.54, 95% confidence interval 1.12-2.12, p=0.008) and found no significant associations for the other polymorphisms. | /"RET"/ polymorphisms and sporadic medullary thyroid carcinoma in a Portuguese population. | The genetic basis of the sporadic form of medullary thyroid carcinoma, derived from "C" cells, is still poorly understood. Somatic mutations of /"RET"/ proto-oncogene have been reported at a variable frequency ranging from 23% to 69%. The hypothesis that low penetrance factors, such as polymorphisms, might contribute to the phenotype of this neoplasm has been addressed in a few studies conducting to conflicting results. Herein, we studied 100 individuals (50 patients and 50 controls) aiming to compare the frequencies of G691S, L769L, S836S, and S904S /"RET"/ polymorphisms observed in patients with respect to controls. Furthermore, meta-analysis of published studies including the present results was conducted. To test the contributory role of the above polymorphisms for the development of "C"-cell /"hyperplasia"/, we studied a group of 10 individuals selected for having a positive pentagastrin test despite the absence of a /"RET"/ germline mutation. An over-representation of the G691S polymorphism, particularly in females, was observed in patients with respect to controls, although not reaching the level of significance. Allelic frequencies of the other three polymorphisms were not different in patients and controls. Results obtained in the admittedly small group of individuals with a positive pentagastrin test are unlikely to support a major influence of any polymorphism in the development of "C"-cell /"hyperplasia"/. The meta-analysis provided evidence for a significant association of the S691 allele with MTC (odds ratio 1.54, 95% confidence interval 1.12-2.12, p=0.008) and found no significant associations for the other polymorphisms. | [
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16234515 | Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. | PURPOSE: The purpose of this study was to estimate the extent of protection offered against breast cancer by prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery. PATIENTS AND METHODS: We analyzed 1,439 patients with breast cancer and 1,866 matched controls derived from a registry of BRCA1 and BRCA2 carriers. We estimated odds ratios (ORs) of breast cancer for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use. RESULTS: A previous history of oophorectomy was associated with a significant reduction in breast cancer risk of 56% for BRCA1 carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for BRCA2 carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for BRCA1 carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57). CONCLUSION: Oophorectomy is an effective means of reducing the risk of breast cancer in carriers of BRCA1 mutations. The data suggest oophorectomy is protective in BRCA2 carriers as well, but needs to be confirmed in other studies. | /"Breast cancer"/ risk following bilateral oophorectomy in /"BRCA1"/ and BRCA2 mutation carriers: an international case-control study. | PURPOSE: The purpose of this study was to estimate the extent of protection offered against /"breast cancer"/ by prophylactic oophorectomy in carriers of /"BRCA1"/ or BRCA2 mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery. PATIENTS AND METHODS: We analyzed 1,439 patients with /"breast cancer"/ and 1,866 matched controls derived from a registry of /"BRCA1"/ and BRCA2 carriers. We estimated odds ratios (ORs) of /"breast cancer"/ for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use. RESULTS: A previous history of oophorectomy was associated with a significant reduction in /"breast cancer"/ risk of 56% for /"BRCA1"/ carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for BRCA2 carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for /"BRCA1"/ carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57). CONCLUSION: Oophorectomy is an effective means of reducing the risk of /"breast cancer"/ in carriers of /"BRCA1"/ mutations. The data suggest oophorectomy is protective in BRCA2 carriers as well, but needs to be confirmed in other studies. | [
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16234515 | Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. | PURPOSE: The purpose of this study was to estimate the extent of protection offered against breast cancer by prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery. PATIENTS AND METHODS: We analyzed 1,439 patients with breast cancer and 1,866 matched controls derived from a registry of BRCA1 and BRCA2 carriers. We estimated odds ratios (ORs) of breast cancer for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use. RESULTS: A previous history of oophorectomy was associated with a significant reduction in breast cancer risk of 56% for BRCA1 carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for BRCA2 carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for BRCA1 carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57). CONCLUSION: Oophorectomy is an effective means of reducing the risk of breast cancer in carriers of BRCA1 mutations. The data suggest oophorectomy is protective in BRCA2 carriers as well, but needs to be confirmed in other studies. | /"Breast cancer"/ risk following bilateral oophorectomy in BRCA1 and /"BRCA2"/ mutation carriers: an international case-control study. | PURPOSE: The purpose of this study was to estimate the extent of protection offered against /"breast cancer"/ by prophylactic oophorectomy in carriers of BRCA1 or /"BRCA2"/ mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery. PATIENTS AND METHODS: We analyzed 1,439 patients with /"breast cancer"/ and 1,866 matched controls derived from a registry of BRCA1 and /"BRCA2"/ carriers. We estimated odds ratios (ORs) of /"breast cancer"/ for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use. RESULTS: A previous history of oophorectomy was associated with a significant reduction in /"breast cancer"/ risk of 56% for BRCA1 carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for /"BRCA2"/ carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for BRCA1 carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57). CONCLUSION: Oophorectomy is an effective means of reducing the risk of /"breast cancer"/ in carriers of BRCA1 mutations. The data suggest oophorectomy is protective in /"BRCA2"/ carriers as well, but needs to be confirmed in other studies. | [
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16254428 | Effect of the apolipoprotein E epsilon4 allele on the efficacy and tolerability of galantamine in the treatment of Alzheimer's disease. | OBJECTIVE: To investigate the effect of the apolipoprotein E (ApoE) epsilon4 allele on the efficacy and tolerability of galantamine treatment. METHODS: A total of 202 patients with mild to moderate Alzheimer's disease participated in a 16-week, prospective, multi-center, randomized, double-blind galantamine trial in a Korean population. Patients were assessed at baseline and after 4, 8 and 16 weeks of randomized treatment using the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia Scale (DAD), the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and adverse events. ApoE genotypes were determined for all subjects. RESULTS: Of the 202 subjects, 115 carried at least one ApoE epsilon4 allele and 87 did not. In both ApoE epsilon4 carriers and ApoE epsilon4 noncarriers, significant improvements were detected relative to baseline on ADAS-cog/11, CIBIC-plus, DAD and BEHAVE-AD. ApoE epsilon4 noncarriers showed better improvement in mean total BEHAVE-AD score and mean psychosis (delusions and hallucinations) subscale score than ApoE epsilon4 carriers. The incidence of weight loss was significantly higher in ApoE epsilon4 carriers (n = 11; 9.6%) than in ApoE epsilon4 noncarriers (n = 1; 1.2%) during this 16-week study, even though 92% of patients who complained of weight loss completed this 16-week trial successfully. CONCLUSION: ApoE epsilon4 genotype does not affect galantamine-related improvements in cognition, global rating, function and behavior. Longer prospective studies with larger patient populations are required to confirm these new findings. | Effect of the /"apolipoprotein E"/ epsilon4 allele on the efficacy and tolerability of galantamine in the treatment of /"Alzheimer's disease"/. | OBJECTIVE: To investigate the effect of the /"apolipoprotein E"/ (/"ApoE"/) epsilon4 allele on the efficacy and tolerability of galantamine treatment. METHODS: A total of 202 patients with mild to moderate /"Alzheimer's disease"/ participated in a 16-week, prospective, multi-center, randomized, double-blind galantamine trial in a Korean population. Patients were assessed at baseline and after 4, 8 and 16 weeks of randomized treatment using the 11-item cognitive subscale of the /"Alzheimer's Disease"/ Assessment Scale (ADAS-cog/11), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia Scale (DAD), the Behavioural Pathology in /"Alzheimer's Disease"/ Rating Scale (BEHAVE-AD) and adverse events. /"ApoE"/ genotypes were determined for all subjects. RESULTS: Of the 202 subjects, 115 carried at least one /"ApoE"/ epsilon4 allele and 87 did not. In both /"ApoE"/ epsilon4 carriers and /"ApoE"/ epsilon4 noncarriers, significant improvements were detected relative to baseline on ADAS-cog/11, CIBIC-plus, DAD and BEHAVE-AD. /"ApoE"/ epsilon4 noncarriers showed better improvement in mean total BEHAVE-AD score and mean psychosis (delusions and hallucinations) subscale score than /"ApoE"/ epsilon4 carriers. The incidence of weight loss was significantly higher in /"ApoE"/ epsilon4 carriers (n = 11; 9.6%) than in /"ApoE"/ epsilon4 noncarriers (n = 1; 1.2%) during this 16-week study, even though 92% of patients who complained of weight loss completed this 16-week trial successfully. CONCLUSION: /"ApoE"/ epsilon4 genotype does not affect galantamine-related improvements in cognition, global rating, function and behavior. Longer prospective studies with larger patient populations are required to confirm these new findings. | [
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16254428 | Effect of the apolipoprotein E epsilon4 allele on the efficacy and tolerability of galantamine in the treatment of Alzheimer's disease. | OBJECTIVE: To investigate the effect of the apolipoprotein E (ApoE) epsilon4 allele on the efficacy and tolerability of galantamine treatment. METHODS: A total of 202 patients with mild to moderate Alzheimer's disease participated in a 16-week, prospective, multi-center, randomized, double-blind galantamine trial in a Korean population. Patients were assessed at baseline and after 4, 8 and 16 weeks of randomized treatment using the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia Scale (DAD), the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and adverse events. ApoE genotypes were determined for all subjects. RESULTS: Of the 202 subjects, 115 carried at least one ApoE epsilon4 allele and 87 did not. In both ApoE epsilon4 carriers and ApoE epsilon4 noncarriers, significant improvements were detected relative to baseline on ADAS-cog/11, CIBIC-plus, DAD and BEHAVE-AD. ApoE epsilon4 noncarriers showed better improvement in mean total BEHAVE-AD score and mean psychosis (delusions and hallucinations) subscale score than ApoE epsilon4 carriers. The incidence of weight loss was significantly higher in ApoE epsilon4 carriers (n = 11; 9.6%) than in ApoE epsilon4 noncarriers (n = 1; 1.2%) during this 16-week study, even though 92% of patients who complained of weight loss completed this 16-week trial successfully. CONCLUSION: ApoE epsilon4 genotype does not affect galantamine-related improvements in cognition, global rating, function and behavior. Longer prospective studies with larger patient populations are required to confirm these new findings. | Effect of the /"apolipoprotein E"/ epsilon4 allele on the efficacy and tolerability of galantamine in the treatment of Alzheimer's disease. | OBJECTIVE: To investigate the effect of the /"apolipoprotein E"/ (/"ApoE"/) epsilon4 allele on the efficacy and tolerability of galantamine treatment. METHODS: A total of 202 patients with mild to moderate Alzheimer's disease participated in a 16-week, prospective, multi-center, randomized, double-blind galantamine trial in a Korean population. Patients were assessed at baseline and after 4, 8 and 16 weeks of randomized treatment using the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia Scale (DAD), the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and adverse events. /"ApoE"/ genotypes were determined for all subjects. RESULTS: Of the 202 subjects, 115 carried at least one /"ApoE"/ epsilon4 allele and 87 did not. In both /"ApoE"/ epsilon4 carriers and /"ApoE"/ epsilon4 noncarriers, significant improvements were detected relative to baseline on ADAS-cog/11, CIBIC-plus, DAD and BEHAVE-AD. /"ApoE"/ epsilon4 noncarriers showed better improvement in mean total BEHAVE-AD score and mean psychosis (delusions and hallucinations) subscale score than /"ApoE"/ epsilon4 carriers. The incidence of /"weight loss"/ was significantly higher in /"ApoE"/ epsilon4 carriers (n = 11; 9.6%) than in /"ApoE"/ epsilon4 noncarriers (n = 1; 1.2%) during this 16-week study, even though 92% of patients who complained of /"weight loss"/ completed this 16-week trial successfully. CONCLUSION: /"ApoE"/ epsilon4 genotype does not affect galantamine-related improvements in cognition, global rating, function and behavior. Longer prospective studies with larger patient populations are required to confirm these new findings. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for Crohn's disease and /"psoriatic arthritis"/. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, /"CARD15"/, was demonstrated to be associated with /"psoriatic arthritis"/ (/"PsA"/). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of /"PsA"/ with Crohn's disease susceptibility genes. METHODS: Association with /"CARD15"/ and OCTN was investigated in UK Caucasian patients with /"PsA"/ (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of /"PsA"/ with /"CARD15"/ was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with /"PsA"/ (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with /"PsA"/ (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with /"PsA"/, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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} | Yes |
16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, /"SLC22A4"/ and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The /"SLC22A4"/ gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with /"psoriasis"/ (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with /"psoriasis"/ alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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} | Yes |
16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for Crohn's disease and /"psoriatic arthritis"/. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with /"psoriatic arthritis"/ (/"PsA"/). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, /"SLC22A4"/ and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The /"SLC22A4"/ gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of /"PsA"/ with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with /"PsA"/ (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of /"PsA"/ with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with /"PsA"/ (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with /"PsA"/ (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with /"PsA"/, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, /"CARD15"/, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with /"CARD15"/ and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with /"psoriasis"/ (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with /"CARD15"/ was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with /"psoriasis"/ alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and /"SLC22A5"/, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with /"psoriasis"/ (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of /"SLC22A5"/ (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with /"psoriasis"/ alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for Crohn's disease and /"psoriatic arthritis"/. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with /"psoriatic arthritis"/ (/"PsA"/). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and /"SLC22A5"/, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of /"PsA"/ with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with /"PsA"/ (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of /"PsA"/ with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of /"SLC22A5"/ (rs2631367) was associated with /"PsA"/ (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with /"PsA"/ (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with /"PsA"/, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for /"Crohn's disease"/ and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a /"Crohn's disease"/ gene, /"CARD15"/, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second /"Crohn's disease"/ susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with /"Crohn's disease"/ susceptibility genes. METHODS: Association with /"CARD15"/ and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with /"Crohn's disease"/, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with /"CARD15"/ was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with /"Crohn's disease"/ was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with /"Crohn's disease"/ is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for /"Crohn's disease"/ and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a /"Crohn's disease"/ gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and /"SLC22A5"/, was identified as a second /"Crohn's disease"/ susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with /"Crohn's disease"/ susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with /"Crohn's disease"/, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of /"SLC22A5"/ (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with /"Crohn's disease"/ was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with /"Crohn's disease"/ is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for /"Crohn's disease"/ and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a /"Crohn's disease"/ gene, /"CARD15"/, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second /"Crohn's disease"/ susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with /"Crohn's disease"/ susceptibility genes. METHODS: Association with /"CARD15"/ and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with /"Crohn's disease"/, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with /"CARD15"/ was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with /"Crohn's disease"/ was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with /"Crohn's disease"/ is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and /"SLC22A5"/, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with /"rheumatoid arthritis"/. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of /"SLC22A5"/ (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of /"inflammation"/ for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie /"inflammatory diseases"/. In a previous study, a Crohn's disease gene, /"CARD15"/, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with /"CARD15"/ and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with /"CARD15"/ was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of /"inflammation"/. | [
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16255050 | Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation. | Evidence for common genetic control in pathways of /"inflammation"/ for Crohn's disease and psoriatic arthritis. | OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie /"inflammatory diseases"/. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, /"SLC22A4"/ and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The /"SLC22A4"/ gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of /"inflammation"/. | [
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} | No |
16257277 | -511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in Paget disease of bone. | INTRODUCTION: Osteoclasts are the most important cells involved in the pathogenesis of Paget disease of bone (PDB). Cytokines stimulate osteoclast differentiation and activation, with some of them over-expressed in pagetic osteoclasts. We have assessed whether genetic variability in genes coding of proteins from the IL1 pathway clustered in chromosome 2 is associated with clinical characteristics and the therapeutic response of patients with PDB. METHODS: We have studied -511 C/T and +3953 T/C polymorphisms of the IL1B gene, a HinfI polymorphism in the 5'UTR of the IL1R1 gene, and a variable number of tandem repeats (VNTR) in the intron 2 of the IL1RN gene, in 165 patients diagnosed as suffering from PDB and in 122 healthy controls. Distribution of genotypes and alleles was studied for association with clinical and laboratory data and response to bisphosphonate (BSP) treatment. RESULTS: No differences were observed in the distribution of genotypes or alleles between PDB patients and control subjects. We also failed to detect differences concerning epidemiological, clinical and laboratory data in the series of PDB patients. However, the -511 CC genotype of the IL1B gene was associated with a higher percentage of resistance to BSP (49% vs. 20%; P = 0.00 for all BSP, 60% vs. 39%, P = 0.17 for etidronate, 50% vs. 37% P = 0.53 for clodronate, 48 vs. 34% P = 0.05 for tiludronate and 50% vs. 4% P = 0.01 for risedronate). CONCLUSIONS: Our results suggest that the -511 CC genotype of the IL1B gene could be related to resistance to bisphosphonates in patients with PDB. | -511 C/T /"IL1B"/ gene polymorphism is associated to resistance to bisphosphonates treatment in /"Paget disease of bone"/. | INTRODUCTION: Osteoclasts are the most important cells involved in the pathogenesis of /"Paget disease of bone"/ (/"PDB"/). Cytokines stimulate osteoclast differentiation and activation, with some of them over-expressed in pagetic osteoclasts. We have assessed whether genetic variability in genes coding of proteins from the /"IL1"/ pathway clustered in chromosome 2 is associated with clinical characteristics and the therapeutic response of patients with /"PDB"/. METHODS: We have studied -511 C/T and +3953 T/C polymorphisms of the /"IL1B"/ gene, a HinfI polymorphism in the 5'UTR of the IL1R1 gene, and a variable number of tandem repeats (VNTR) in the intron 2 of the IL1RN gene, in 165 patients diagnosed as suffering from /"PDB"/ and in 122 healthy controls. Distribution of genotypes and alleles was studied for association with clinical and laboratory data and response to bisphosphonate (BSP) treatment. RESULTS: No differences were observed in the distribution of genotypes or alleles between /"PDB"/ patients and control subjects. We also failed to detect differences concerning epidemiological, clinical and laboratory data in the series of /"PDB"/ patients. However, the -511 CC genotype of the /"IL1B"/ gene was associated with a higher percentage of resistance to BSP (49% vs. 20%; P = 0.00 for all BSP, 60% vs. 39%, P = 0.17 for etidronate, 50% vs. 37% P = 0.53 for clodronate, 48 vs. 34% P = 0.05 for tiludronate and 50% vs. 4% P = 0.01 for risedronate). CONCLUSIONS: Our results suggest that the -511 CC genotype of the /"IL1B"/ gene could be related to resistance to bisphosphonates in patients with /"PDB"/. | [
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16257277 | -511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in Paget disease of bone. | INTRODUCTION: Osteoclasts are the most important cells involved in the pathogenesis of Paget disease of bone (PDB). Cytokines stimulate osteoclast differentiation and activation, with some of them over-expressed in pagetic osteoclasts. We have assessed whether genetic variability in genes coding of proteins from the IL1 pathway clustered in chromosome 2 is associated with clinical characteristics and the therapeutic response of patients with PDB. METHODS: We have studied -511 C/T and +3953 T/C polymorphisms of the IL1B gene, a HinfI polymorphism in the 5'UTR of the IL1R1 gene, and a variable number of tandem repeats (VNTR) in the intron 2 of the IL1RN gene, in 165 patients diagnosed as suffering from PDB and in 122 healthy controls. Distribution of genotypes and alleles was studied for association with clinical and laboratory data and response to bisphosphonate (BSP) treatment. RESULTS: No differences were observed in the distribution of genotypes or alleles between PDB patients and control subjects. We also failed to detect differences concerning epidemiological, clinical and laboratory data in the series of PDB patients. However, the -511 CC genotype of the IL1B gene was associated with a higher percentage of resistance to BSP (49% vs. 20%; P = 0.00 for all BSP, 60% vs. 39%, P = 0.17 for etidronate, 50% vs. 37% P = 0.53 for clodronate, 48 vs. 34% P = 0.05 for tiludronate and 50% vs. 4% P = 0.01 for risedronate). CONCLUSIONS: Our results suggest that the -511 CC genotype of the IL1B gene could be related to resistance to bisphosphonates in patients with PDB. | -511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in /"Paget disease of bone"/. | INTRODUCTION: Osteoclasts are the most important cells involved in the pathogenesis of /"Paget disease of bone"/ (/"PDB"/). Cytokines stimulate osteoclast differentiation and activation, with some of them over-expressed in pagetic osteoclasts. We have assessed whether genetic variability in genes coding of proteins from the IL1 pathway clustered in chromosome 2 is associated with clinical characteristics and the therapeutic response of patients with /"PDB"/. METHODS: We have studied -511 C/T and +3953 T/C polymorphisms of the IL1B gene, a HinfI polymorphism in the 5'UTR of the /"IL1R1"/ gene, and a variable number of tandem repeats (VNTR) in the intron 2 of the IL1RN gene, in 165 patients diagnosed as suffering from /"PDB"/ and in 122 healthy controls. Distribution of genotypes and alleles was studied for association with clinical and laboratory data and response to bisphosphonate (BSP) treatment. RESULTS: No differences were observed in the distribution of genotypes or alleles between /"PDB"/ patients and control subjects. We also failed to detect differences concerning epidemiological, clinical and laboratory data in the series of /"PDB"/ patients. However, the -511 CC genotype of the IL1B gene was associated with a higher percentage of resistance to BSP (49% vs. 20%; P = 0.00 for all BSP, 60% vs. 39%, P = 0.17 for etidronate, 50% vs. 37% P = 0.53 for clodronate, 48 vs. 34% P = 0.05 for tiludronate and 50% vs. 4% P = 0.01 for risedronate). CONCLUSIONS: Our results suggest that the -511 CC genotype of the IL1B gene could be related to resistance to bisphosphonates in patients with /"PDB"/. | [
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16259952 | GATA4-mediated cardiac hypertrophy induced by d-myo-inositol 1,4,5-tris-phosphate. | We evaluated the effects of d-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. d-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, beta-myosin heavy chain, and alpha-actin. The administration of d-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that d-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of d-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that d-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway. | /"GATA4"/-mediated /"cardiac hypertrophy"/ induced by d-myo-inositol 1,4,5-tris-phosphate. | We evaluated the effects of d-myo-inositol 1,4,5-tris-phosphate on /"cardiac hypertrophy"/. d-myo-inositol 1,4,5-tris-phosphate augmented /"cardiac hypertrophy"/ as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, beta-myosin heavy chain, and alpha-actin. The administration of d-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (/"GATA4"/). Real-time quantitative RT-PCR showed that d-myo-inositol 1,4,5-tris-phosphate-induced /"GATA4"/ mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of d-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that d-myo-inositol 1,4,5-tris-phosphate-induced /"cardiac hypertrophy"/ is mediated by /"GATA4"/ but independent from the calcineurin pathway. | [
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16259952 | GATA4-mediated cardiac hypertrophy induced by d-myo-inositol 1,4,5-tris-phosphate. | We evaluated the effects of d-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. d-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, beta-myosin heavy chain, and alpha-actin. The administration of d-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that d-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of d-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that d-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway. | GATA4-mediated /"cardiac hypertrophy"/ induced by d-myo-inositol 1,4,5-tris-phosphate. | We evaluated the effects of d-myo-inositol 1,4,5-tris-phosphate on /"cardiac hypertrophy"/. d-myo-inositol 1,4,5-tris-phosphate augmented /"cardiac hypertrophy"/ as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, beta-myosin heavy chain, and alpha-actin. The administration of d-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that d-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the /"calcineurin inhibitor"/, cyclosporine A. The effect of d-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that d-myo-inositol 1,4,5-tris-phosphate-induced /"cardiac hypertrophy"/ is mediated by GATA4 but independent from the calcineurin pathway. | [
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16277672 | Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the protein tyrosine phosphatase nonreceptor 22-620W allele. | The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early T-cell activation. An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other autoimmune diseases. Expected linkage proof for consistency cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was therefore to search for linkage evidence with the transmission disequilibrium test. DNA from the French Caucasian population was available for two samples of 100 families with one RA patient and both parents, and for 88 RA index cases from RA ASP families. Genotyping was carried out by PCR-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, genotype relative risk and ASP-based analysis. The transmission disequilibrium test of the PTPN22-620W allele revealed linkage and association for RF+ RA (61% of transmission, P = 0.037). The genotype relative risk showed the risk allele in 34% of RF+ RA patients and in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence interval = 1.03-2.78). The ASP investigation showed no enriched risk allele in RA multiplex families, resulting in a lack of power of ASP analysis, explaining the published negative results. This study is the first to show linkage of PTPN22 to RF+ RA, consistent with PTPN22 as a new RA gene. | /"Rheumatoid arthritis"/ seropositive for the rheumatoid factor is linked to the protein tyrosine phosphatase nonreceptor 22-620W allele. | The /"protein tyrosine phosphatase nonreceptor type 22"/ (/"PTPN22"/) gene encodes for lymphoid tyrosine phosphatase /"LYP"/, involved in the negative regulation of early T-cell activation. An association has recently been reported between the /"PTPN22"/-620W functional allele and rheumatoid factor-positive (RF+) /"rheumatoid arthritis"/ (/"RA"/), among other autoimmune diseases. Expected linkage proof for consistency cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was therefore to search for linkage evidence with the transmission disequilibrium test. DNA from the French Caucasian population was available for two samples of 100 families with one /"RA"/ patient and both parents, and for 88 /"RA"/ index cases from /"RA"/ ASP families. Genotyping was carried out by PCR-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, genotype relative risk and ASP-based analysis. The transmission disequilibrium test of the /"PTPN22"/-620W allele revealed linkage and association for RF+ /"RA"/ (61% of transmission, P = 0.037). The genotype relative risk showed the risk allele in 34% of RF+ /"RA"/ patients and in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence interval = 1.03-2.78). The ASP investigation showed no enriched risk allele in /"RA"/ multiplex families, resulting in a lack of power of ASP analysis, explaining the published negative results. This study is the first to show linkage of /"PTPN22"/ to RF+ /"RA"/, consistent with /"PTPN22"/ as a new /"RA"/ gene. | [
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16277672 | Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the protein tyrosine phosphatase nonreceptor 22-620W allele. | The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early T-cell activation. An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other autoimmune diseases. Expected linkage proof for consistency cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was therefore to search for linkage evidence with the transmission disequilibrium test. DNA from the French Caucasian population was available for two samples of 100 families with one RA patient and both parents, and for 88 RA index cases from RA ASP families. Genotyping was carried out by PCR-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, genotype relative risk and ASP-based analysis. The transmission disequilibrium test of the PTPN22-620W allele revealed linkage and association for RF+ RA (61% of transmission, P = 0.037). The genotype relative risk showed the risk allele in 34% of RF+ RA patients and in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence interval = 1.03-2.78). The ASP investigation showed no enriched risk allele in RA multiplex families, resulting in a lack of power of ASP analysis, explaining the published negative results. This study is the first to show linkage of PTPN22 to RF+ RA, consistent with PTPN22 as a new RA gene. | Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the protein tyrosine phosphatase nonreceptor 22-620W allele. | The /"protein tyrosine phosphatase nonreceptor type 22"/ (/"PTPN22"/) gene encodes for lymphoid tyrosine phosphatase /"LYP"/, involved in the negative regulation of early T-cell activation. An association has recently been reported between the /"PTPN22"/-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other /"autoimmune diseases"/. Expected linkage proof for consistency cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was therefore to search for linkage evidence with the transmission disequilibrium test. DNA from the French Caucasian population was available for two samples of 100 families with one RA patient and both parents, and for 88 RA index cases from RA ASP families. Genotyping was carried out by PCR-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, genotype relative risk and ASP-based analysis. The transmission disequilibrium test of the /"PTPN22"/-620W allele revealed linkage and association for RF+ RA (61% of transmission, P = 0.037). The genotype relative risk showed the risk allele in 34% of RF+ RA patients and in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence interval = 1.03-2.78). The ASP investigation showed no enriched risk allele in RA multiplex families, resulting in a lack of power of ASP analysis, explaining the published negative results. This study is the first to show linkage of /"PTPN22"/ to RF+ RA, consistent with /"PTPN22"/ as a new RA gene. | [
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} | No |
16299685 | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | /"Interleukin-6"/ (/"IL-6"/) -174 G/C polymorphism in /"familial Mediterranean fever"/ patients with and without amyloidosis. | /"Familial Mediterranean fever"/ (/"FMF"/) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, /"IL-6"/ and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important /"IL-6"/ -174 G/C polymorphism in the clinical outcome of /"FMF"/ and amyloidosis. One hundred and fifty-six /"FMF"/ patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that /"IL-6"/ -174 G/C polymorphism is not associated with /"FMF"/ and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | [
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} | Yes |
16299685 | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without /"amyloidosis"/. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and /"tumor necrosis factor-alpha"/ (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and /"amyloidosis"/. One hundred and fifty-six FMF patients (80 with /"amyloidosis"/) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and /"amyloidosis"/. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | [
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} | Yes |
16299685 | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | /"Interleukin-6"/ (/"IL-6"/) -174 G/C polymorphism in familial Mediterranean fever patients with and without /"amyloidosis"/. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, /"IL-6"/ and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important /"IL-6"/ -174 G/C polymorphism in the clinical outcome of FMF and /"amyloidosis"/. One hundred and fifty-six FMF patients (80 with /"amyloidosis"/) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that /"IL-6"/ -174 G/C polymorphism is not associated with FMF and /"amyloidosis"/. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | [
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16299685 | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | Interleukin-6 (IL-6) -174 G/C polymorphism in /"familial Mediterranean fever"/ patients with and without amyloidosis. | /"Familial Mediterranean fever"/ (/"FMF"/) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and /"tumor necrosis factor-alpha"/ (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of /"FMF"/ and amyloidosis. One hundred and fifty-six /"FMF"/ patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with /"FMF"/ and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | [
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16299685 | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | /"Interleukin-6"/ (/"IL-6"/) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of /"fever"/ and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, /"IL-6"/ and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important /"IL-6"/ -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that /"IL-6"/ -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | [
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16299685 | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | /"Interleukin-6"/ (/"IL-6"/) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and /"inflammation"/. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, /"IL-6"/ and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important /"IL-6"/ -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that /"IL-6"/ -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | [
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16299685 | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | /"Interleukin-6"/ (/"IL-6"/) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of /"fever"/ and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, /"IL-6"/ and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important /"IL-6"/ -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that /"IL-6"/ -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | [
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16299685 | Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | /"Interleukin-6"/ (/"IL-6"/) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis. | Familial Mediterranean fever (FMF) is a /"recessive disorder"/ characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, /"IL-6"/ and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important /"IL-6"/ -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that /"IL-6"/ -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease. | [
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16309832 | The cyclooxygenase 2 -765 C promoter allele is a protective factor for Alzheimer's disease. | The cyclooxygenase-2 enzyme (COX-2) is of particular importance in the inflammatory response and recent findings have demonstrated a considerable role in Alzheimer's disease (AD) pathogenesis. In order to assess the possible putative role of a COX-2 polymorphism (765G/C) in AD, we examined its distribution in 161 community-based controls and 168 AD clinic-based cases previously recruited from memory disorder clinics in Tampa and Miami, Florida. There were no significant differences between the two groups in age/age of onset or gender. A significant difference was observed in the distribution of the COX-2 -765 alleles between AD cases and controls (chi(2) = 6.565, p = .010; OR = .596; CI = [.401-.888], p = .011), with the frequency of the C allele being higher in controls. In addition, a significant difference was observed for this polymorphism by genotype (chi(2) = 6.561, p = .038) and by presence or absence of C+ genotypes (chi(2) = 6.207, p = .013; OR = .464, CI = [.351-.885], p = .013). In this sample, the C allele of COX-2 -765 promoter polymorphism is associated with decreased risk of Alzheimer's disease, a finding which further supports the involvement of COX-2 in AD etiology. | The /"cyclooxygenase 2"/ -765 C promoter allele is a protective factor for /"Alzheimer's disease"/. | The cyclooxygenase-2 enzyme (COX-2) is of particular importance in the inflammatory response and recent findings have demonstrated a considerable role in /"Alzheimer's disease"/ (/"AD"/) pathogenesis. In order to assess the possible putative role of a COX-2 polymorphism (765G/C) in /"AD"/, we examined its distribution in 161 community-based controls and 168 /"AD"/ clinic-based cases previously recruited from memory disorder clinics in Tampa and Miami, Florida. There were no significant differences between the two groups in age/age of onset or gender. A significant difference was observed in the distribution of the COX-2 -765 alleles between /"AD"/ cases and controls (chi(2) = 6.565, p = .010; OR = .596; CI = [.401-.888], p = .011), with the frequency of the C allele being higher in controls. In addition, a significant difference was observed for this polymorphism by genotype (chi(2) = 6.561, p = .038) and by presence or absence of C+ genotypes (chi(2) = 6.207, p = .013; OR = .464, CI = [.351-.885], p = .013). In this sample, the C allele of COX-2 -765 promoter polymorphism is associated with decreased risk of /"Alzheimer's disease"/, a finding which further supports the involvement of COX-2 in /"AD"/ etiology. | [
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16309832 | The cyclooxygenase 2 -765 C promoter allele is a protective factor for Alzheimer's disease. | The cyclooxygenase-2 enzyme (COX-2) is of particular importance in the inflammatory response and recent findings have demonstrated a considerable role in Alzheimer's disease (AD) pathogenesis. In order to assess the possible putative role of a COX-2 polymorphism (765G/C) in AD, we examined its distribution in 161 community-based controls and 168 AD clinic-based cases previously recruited from memory disorder clinics in Tampa and Miami, Florida. There were no significant differences between the two groups in age/age of onset or gender. A significant difference was observed in the distribution of the COX-2 -765 alleles between AD cases and controls (chi(2) = 6.565, p = .010; OR = .596; CI = [.401-.888], p = .011), with the frequency of the C allele being higher in controls. In addition, a significant difference was observed for this polymorphism by genotype (chi(2) = 6.561, p = .038) and by presence or absence of C+ genotypes (chi(2) = 6.207, p = .013; OR = .464, CI = [.351-.885], p = .013). In this sample, the C allele of COX-2 -765 promoter polymorphism is associated with decreased risk of Alzheimer's disease, a finding which further supports the involvement of COX-2 in AD etiology. | The /"cyclooxygenase 2"/ -765 C promoter allele is a protective factor for Alzheimer's disease. | The cyclooxygenase-2 enzyme (COX-2) is of particular importance in the inflammatory response and recent findings have demonstrated a considerable role in Alzheimer's disease (AD) pathogenesis. In order to assess the possible putative role of a COX-2 polymorphism (765G/C) in AD, we examined its distribution in 161 community-based controls and 168 AD clinic-based cases previously recruited from /"memory disorder"/ clinics in Tampa and Miami, Florida. There were no significant differences between the two groups in age/age of onset or gender. A significant difference was observed in the distribution of the COX-2 -765 alleles between AD cases and controls (chi(2) = 6.565, p = .010; OR = .596; CI = [.401-.888], p = .011), with the frequency of the C allele being higher in controls. In addition, a significant difference was observed for this polymorphism by genotype (chi(2) = 6.561, p = .038) and by presence or absence of C+ genotypes (chi(2) = 6.207, p = .013; OR = .464, CI = [.351-.885], p = .013). In this sample, the C allele of COX-2 -765 promoter polymorphism is associated with decreased risk of Alzheimer's disease, a finding which further supports the involvement of COX-2 in AD etiology. | [
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16313808 | [The research on the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter with its effect of preventing ESRD patients from microinflammation and arteriosclerosis]. | OBJECTIVE: We do this investigation in order to reveal the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter, and end stage renal disease (ESRD) patients microinflammatory state and arteriosclerosis (AS). METHODS: We used PCR-RFLP to measure the various kinds of distribution of IL-10 gene-1082A/G genotype and relevant indexes of microinflammatory state and AS of 870 ESRD patients and 1000 healthy persons of control group and to analyze the mechanism of its protection effect keeping ESRD patients away from microinflammation and arteriosclerosis. RESULTS: Compared with the control group, CRP, TNF-alpha, CH50, C3, IL-10 and Alb of ESRD group were in the normal range, but still significantly higher than those of the control group, while IL-10, Alb were significant lower (P < 0.05). The genotype distribution and allele frequency of IL-10A/G gene had no significant differences between the healthy group and the control group (P > 0.05). Levels of CRP, TNF-alpha, CH50 and C3 of ESRD patients with IL-10A/A genotype were significantly higher than those of ESRD patients with G/G and G/A genotype (P < 0.05), while IL-10 and Alb were significantly lower (P < 0.01). The production of IL-10 in serum from patients with IL-10A/A genotype was significantly lower than that of patients with G/G and G/A genotype (P < 0.01). The incidence rate of AS of patients with IL-10-1082A/A genotype was significantly higher than that of patients with G/G and G/A genotype (P < 0.01). The raise of AS incidence rate was correspondent with the decline of serum IL-10 and raise of serum CRP and Fib. CONCLUSION: The IL-10A/A genotype is a predictable factor of microinflammatory state and high AS incidence rate in ESRD patients. We use IL-10G/G genotype to modulate the high production of serum IL-10, to decline inflammatory reaction and to keep away from microinflammation and AS in ESRD patients. We should work hard on improving the dialysis membrane to reduce the anti-inflammatory factors in uremia for chronic renal failure patients with high arteriosclerosis risk. | [The research on the relationship between the polymorphism of 1082A/G, anti-inflammatory /"interleukin-10"/ gene promoter with its effect of preventing ESRD patients from microinflammation and /"arteriosclerosis"/]. | OBJECTIVE: We do this investigation in order to reveal the relationship between the polymorphism of 1082A/G, anti-inflammatory /"interleukin-10"/ gene promoter, and end stage renal disease (ESRD) patients /"microinflammatory state and arteriosclerosis"/ (/"AS"/). METHODS: We used PCR-RFLP to measure the various kinds of distribution of /"IL-10"/ gene-1082A/G genotype and relevant indexes of microinflammatory state and /"AS"/ of 870 ESRD patients and 1000 healthy persons of control group and to analyze the mechanism of its protection effect keeping ESRD patients away from microinflammation and /"arteriosclerosis"/. RESULTS: Compared with the control group, CRP, TNF-alpha, CH50, C3, /"IL-10"/ and Alb of ESRD group were in the normal range, but still significantly higher than those of the control group, while /"IL-10"/, Alb were significant lower (P < 0.05). The genotype distribution and allele frequency of /"IL-10A/G"/ gene had no significant differences between the healthy group and the control group (P > 0.05). Levels of CRP, TNF-alpha, CH50 and C3 of ESRD patients with /"IL-10A"//A genotype were significantly higher than those of ESRD patients with G/G and G/A genotype (P < 0.05), while /"IL-10"/ and Alb were significantly lower (P < 0.01). The production of /"IL-10"/ in serum from patients with /"IL-10A"//A genotype was significantly lower than that of patients with G/G and G/A genotype (P < 0.01). The incidence rate of /"AS"/ of patients with /"IL-10"/-1082A/A genotype was significantly higher than that of patients with G/G and G/A genotype (P < 0.01). The raise of /"AS"/ incidence rate was correspondent with the decline of serum /"IL-10"/ and raise of serum CRP and Fib. CONCLUSION: The /"IL-10A"//A genotype is a predictable factor of microinflammatory state and high /"AS"/ incidence rate in ESRD patients. We use IL-10G/G genotype to modulate the high production of serum /"IL-10"/, to decline inflammatory reaction and to keep away from microinflammation and /"AS"/ in ESRD patients. We should work hard on improving the dialysis membrane to reduce the anti-inflammatory factors in uremia for chronic renal failure patients with high /"arteriosclerosis"/ risk. | [
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16313808 | [The research on the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter with its effect of preventing ESRD patients from microinflammation and arteriosclerosis]. | OBJECTIVE: We do this investigation in order to reveal the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter, and end stage renal disease (ESRD) patients microinflammatory state and arteriosclerosis (AS). METHODS: We used PCR-RFLP to measure the various kinds of distribution of IL-10 gene-1082A/G genotype and relevant indexes of microinflammatory state and AS of 870 ESRD patients and 1000 healthy persons of control group and to analyze the mechanism of its protection effect keeping ESRD patients away from microinflammation and arteriosclerosis. RESULTS: Compared with the control group, CRP, TNF-alpha, CH50, C3, IL-10 and Alb of ESRD group were in the normal range, but still significantly higher than those of the control group, while IL-10, Alb were significant lower (P < 0.05). The genotype distribution and allele frequency of IL-10A/G gene had no significant differences between the healthy group and the control group (P > 0.05). Levels of CRP, TNF-alpha, CH50 and C3 of ESRD patients with IL-10A/A genotype were significantly higher than those of ESRD patients with G/G and G/A genotype (P < 0.05), while IL-10 and Alb were significantly lower (P < 0.01). The production of IL-10 in serum from patients with IL-10A/A genotype was significantly lower than that of patients with G/G and G/A genotype (P < 0.01). The incidence rate of AS of patients with IL-10-1082A/A genotype was significantly higher than that of patients with G/G and G/A genotype (P < 0.01). The raise of AS incidence rate was correspondent with the decline of serum IL-10 and raise of serum CRP and Fib. CONCLUSION: The IL-10A/A genotype is a predictable factor of microinflammatory state and high AS incidence rate in ESRD patients. We use IL-10G/G genotype to modulate the high production of serum IL-10, to decline inflammatory reaction and to keep away from microinflammation and AS in ESRD patients. We should work hard on improving the dialysis membrane to reduce the anti-inflammatory factors in uremia for chronic renal failure patients with high arteriosclerosis risk. | [The research on the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter with its effect of preventing /"ESRD"/ patients from microinflammation and arteriosclerosis]. | OBJECTIVE: We do this investigation in order to reveal the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter, and /"end stage renal disease"/ (/"ESRD"/) patients microinflammatory state and arteriosclerosis (AS). METHODS: We used PCR-RFLP to measure the various kinds of distribution of IL-10 gene-1082A/G genotype and relevant indexes of microinflammatory state and AS of 870 /"ESRD"/ patients and 1000 healthy persons of control group and to analyze the mechanism of its protection effect keeping /"ESRD"/ patients away from microinflammation and arteriosclerosis. RESULTS: Compared with the control group, /"CRP"/, TNF-alpha, CH50, C3, IL-10 and Alb of /"ESRD"/ group were in the normal range, but still significantly higher than those of the control group, while IL-10, Alb were significant lower (P < 0.05). The genotype distribution and allele frequency of IL-10A/G gene had no significant differences between the healthy group and the control group (P > 0.05). Levels of /"CRP"/, TNF-alpha, CH50 and C3 of /"ESRD"/ patients with IL-10A/A genotype were significantly higher than those of /"ESRD"/ patients with G/G and G/A genotype (P < 0.05), while IL-10 and Alb were significantly lower (P < 0.01). The production of IL-10 in serum from patients with IL-10A/A genotype was significantly lower than that of patients with G/G and G/A genotype (P < 0.01). The incidence rate of AS of patients with IL-10-1082A/A genotype was significantly higher than that of patients with G/G and G/A genotype (P < 0.01). The raise of AS incidence rate was correspondent with the decline of serum IL-10 and raise of serum /"CRP"/ and Fib. CONCLUSION: The IL-10A/A genotype is a predictable factor of microinflammatory state and high AS incidence rate in /"ESRD"/ patients. We use IL-10G/G genotype to modulate the high production of serum IL-10, to decline inflammatory reaction and to keep away from microinflammation and AS in /"ESRD"/ patients. We should work hard on improving the dialysis membrane to reduce the anti-inflammatory factors in uremia for chronic renal failure patients with high arteriosclerosis risk. | [
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16318816 | [Polymorphism of metabolic gene and genetic susceptibility to prostate cancer]. | OBJECTIVE: To study the possible relationship between the single nucleotide polymorphism (SNP) of cytochrome P-450 CYP1A1 (CYP1A1) m1, m2 and GSTM1 [null] genotype and genetic susceptibility to prostate cancer (PC). METHODS: Eighty-three PC patients and 115 age-matched healthy controls were enrolled in this study. All DNA samples from peripheral blood were genotyped for genetic polymorphisms of CYP1A1 and GSTM1 genes by genechip technique. RESULTS: There was a significant difference in the frequency of GSTM1 [null] genotype in PC cases (57.8%) compared to healthy controls (41.7%) (chi(2) = 4.99, P = 0.025). Individuals with the GSTM1 [null] genotype demonstrated increased risk (OR = 1.9, 95% CI = 1.10-1.34). The frequency of the GSTM1 [null] genotype was also higher in patients with advanced stage or high grade disease. There were no significant differences in the frequent distribution of two locate of CYP1A1 polymorphisms between prostate cancer patients and healthy controls (P > 0.05). CONCLUSIONS: GSTM1 [null] genotype may be linked to prostate cancer risk in Chinese population. GSTM1 [null] genotype was also related to the stage and grade, which may be helpful in determining the risk of locally disease and advanced PC. | [Polymorphism of metabolic gene and genetic susceptibility to /"prostate cancer"/]. | OBJECTIVE: To study the possible relationship between the single nucleotide polymorphism (SNP) of /"cytochrome P-450 CYP1A1"/ (/"CYP1A1"/) m1, m2 and GSTM1 [null] genotype and genetic susceptibility to /"prostate cancer"/ (/"PC"/). METHODS: Eighty-three /"PC"/ patients and 115 age-matched healthy controls were enrolled in this study. All DNA samples from peripheral blood were genotyped for genetic polymorphisms of /"CYP1A1"/ and GSTM1 genes by genechip technique. RESULTS: There was a significant difference in the frequency of GSTM1 [null] genotype in /"PC"/ cases (57.8%) compared to healthy controls (41.7%) (chi(2) = 4.99, P = 0.025). Individuals with the GSTM1 [null] genotype demonstrated increased risk (OR = 1.9, 95% CI = 1.10-1.34). The frequency of the GSTM1 [null] genotype was also higher in patients with advanced stage or high grade disease. There were no significant differences in the frequent distribution of two locate of /"CYP1A1"/ polymorphisms between /"prostate cancer"/ patients and healthy controls (P > 0.05). CONCLUSIONS: GSTM1 [null] genotype may be linked to /"prostate cancer"/ risk in Chinese population. GSTM1 [null] genotype was also related to the stage and grade, which may be helpful in determining the risk of locally disease and advanced /"PC"/. | [
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16318816 | [Polymorphism of metabolic gene and genetic susceptibility to prostate cancer]. | OBJECTIVE: To study the possible relationship between the single nucleotide polymorphism (SNP) of cytochrome P-450 CYP1A1 (CYP1A1) m1, m2 and GSTM1 [null] genotype and genetic susceptibility to prostate cancer (PC). METHODS: Eighty-three PC patients and 115 age-matched healthy controls were enrolled in this study. All DNA samples from peripheral blood were genotyped for genetic polymorphisms of CYP1A1 and GSTM1 genes by genechip technique. RESULTS: There was a significant difference in the frequency of GSTM1 [null] genotype in PC cases (57.8%) compared to healthy controls (41.7%) (chi(2) = 4.99, P = 0.025). Individuals with the GSTM1 [null] genotype demonstrated increased risk (OR = 1.9, 95% CI = 1.10-1.34). The frequency of the GSTM1 [null] genotype was also higher in patients with advanced stage or high grade disease. There were no significant differences in the frequent distribution of two locate of CYP1A1 polymorphisms between prostate cancer patients and healthy controls (P > 0.05). CONCLUSIONS: GSTM1 [null] genotype may be linked to prostate cancer risk in Chinese population. GSTM1 [null] genotype was also related to the stage and grade, which may be helpful in determining the risk of locally disease and advanced PC. | [Polymorphism of metabolic gene and genetic susceptibility to /"prostate cancer"/]. | OBJECTIVE: To study the possible relationship between the single nucleotide polymorphism (SNP) of cytochrome P-450 CYP1A1 (CYP1A1) m1, m2 and /"GSTM1"/ [null] genotype and genetic susceptibility to /"prostate cancer"/ (/"PC"/). METHODS: Eighty-three /"PC"/ patients and 115 age-matched healthy controls were enrolled in this study. All DNA samples from peripheral blood were genotyped for genetic polymorphisms of CYP1A1 and /"GSTM1"/ genes by genechip technique. RESULTS: There was a significant difference in the frequency of /"GSTM1"/ [null] genotype in /"PC"/ cases (57.8%) compared to healthy controls (41.7%) (chi(2) = 4.99, P = 0.025). Individuals with the /"GSTM1"/ [null] genotype demonstrated increased risk (OR = 1.9, 95% CI = 1.10-1.34). The frequency of the /"GSTM1"/ [null] genotype was also higher in patients with advanced stage or high grade disease. There were no significant differences in the frequent distribution of two locate of CYP1A1 polymorphisms between /"prostate cancer"/ patients and healthy controls (P > 0.05). CONCLUSIONS: /"GSTM1"/ [null] genotype may be linked to /"prostate cancer"/ risk in Chinese population. /"GSTM1"/ [null] genotype was also related to the stage and grade, which may be helpful in determining the risk of locally disease and advanced /"PC"/. | [
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16320352 | The PTPN22 620W allele is a risk factor for Wegener's granulomatosis. | OBJECTIVE: Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the PTPN22 protein appears to herald the development of autoantibodies in these disorders. This study therefore examined whether the functionally relevant PTPN22 polymorphism is associated with Wegener's granulomatosis (WG). METHODS: A population-based study was performed for the PTPN22 polymorphism in 199 patients with WG and in 399 healthy individuals. The R620W variation was investigated by simple restriction fragment-length polymorphism analysis. RESULTS: The PTPN22 620W allele frequency was significantly increased in antineutrophil cytoplasmic antibody (ANCA)-positive WG patients compared with healthy controls (P < 0.001). The association was particularly striking in patients with kidney, lung, eye, and peripheral nervous system involvement (i.e., those with generalized WG). CONCLUSION: The PTPN22 620W allele appears to be involved in the pathogenesis of WG, and ANCA positivity seems to be the hallmark. | The /"PTPN22"/ 620W allele is a risk factor for /"Wegener's granulomatosis"/. | OBJECTIVE: Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene /"PTPN22"/ as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the /"PTPN22"/ protein appears to herald the development of autoantibodies in these disorders. This study therefore examined whether the functionally relevant /"PTPN22"/ polymorphism is associated with /"Wegener's granulomatosis"/ (/"WG"/). METHODS: A population-based study was performed for the /"PTPN22"/ polymorphism in 199 patients with /"WG"/ and in 399 healthy individuals. The R620W variation was investigated by simple restriction fragment-length polymorphism analysis. RESULTS: The /"PTPN22"/ 620W allele frequency was significantly increased in antineutrophil cytoplasmic antibody (ANCA)-positive /"WG"/ patients compared with healthy controls (P < 0.001). The association was particularly striking in patients with kidney, lung, eye, and peripheral nervous system involvement (i.e., those with generalized /"WG"/). CONCLUSION: The /"PTPN22"/ 620W allele appears to be involved in the pathogenesis of /"WG"/, and ANCA positivity seems to be the hallmark. | [
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} | Yes |
16320352 | The PTPN22 620W allele is a risk factor for Wegener's granulomatosis. | OBJECTIVE: Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the PTPN22 protein appears to herald the development of autoantibodies in these disorders. This study therefore examined whether the functionally relevant PTPN22 polymorphism is associated with Wegener's granulomatosis (WG). METHODS: A population-based study was performed for the PTPN22 polymorphism in 199 patients with WG and in 399 healthy individuals. The R620W variation was investigated by simple restriction fragment-length polymorphism analysis. RESULTS: The PTPN22 620W allele frequency was significantly increased in antineutrophil cytoplasmic antibody (ANCA)-positive WG patients compared with healthy controls (P < 0.001). The association was particularly striking in patients with kidney, lung, eye, and peripheral nervous system involvement (i.e., those with generalized WG). CONCLUSION: The PTPN22 620W allele appears to be involved in the pathogenesis of WG, and ANCA positivity seems to be the hallmark. | The /"PTPN22"/ 620W allele is a risk factor for Wegener's granulomatosis. | OBJECTIVE: Analyses of families with multiple autoimmune disorders have revealed a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene /"PTPN22"/ as a predisposing factor for type 1 diabetes, /"seropositive rheumatoid arthritis"/, systemic lupus erythematosus, and Hashimoto thyroiditis, and the presence of the /"PTPN22"/ protein appears to herald the development of autoantibodies in these disorders. This study therefore examined whether the functionally relevant /"PTPN22"/ polymorphism is associated with Wegener's granulomatosis (WG). METHODS: A population-based study was performed for the /"PTPN22"/ polymorphism in 199 patients with WG and in 399 healthy individuals. The R620W variation was investigated by simple restriction fragment-length polymorphism analysis. RESULTS: The /"PTPN22"/ 620W allele frequency was significantly increased in antineutrophil cytoplasmic antibody (ANCA)-positive WG patients compared with healthy controls (P < 0.001). The association was particularly striking in patients with kidney, lung, eye, and peripheral nervous system involvement (i.e., those with generalized WG). CONCLUSION: The /"PTPN22"/ 620W allele appears to be involved in the pathogenesis of WG, and ANCA positivity seems to be the hallmark. | [
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16322490 | Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. | BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). TNF-alpha-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. CONCLUSIONS: A TNF-alpha SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study. | /"Tumor necrosis factor-alpha"/-238G>A promoter polymorphism is associated with increased risk of new /"hemorrhage"/ in the natural course of patients with brain arteriovenous malformations. | BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; /"IL-6-572G>C) and tumor necrosis factor-alpha"/ (/"TNF-alpha"/-238G>A; /"TNF-alpha"/-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). /"TNF-alpha"/-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with /"TNF-alpha"/-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. CONCLUSIONS: A /"TNF-alpha"/ SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study. | [
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} | Yes |
16322490 | Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. | BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). TNF-alpha-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. CONCLUSIONS: A TNF-alpha SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study. | /"Tumor necrosis factor-alpha"/-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with /"brain arteriovenous malformations"/. | BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after /"brain arteriovenous malformation"/ (/"BAVM"/) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with /"BAVM"/ were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any /"BAVM"/ treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; /"IL-6-572G>C) and tumor necrosis factor-alpha"/ (/"TNF-alpha"/-238G>A; /"TNF-alpha"/-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). /"TNF-alpha"/-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with /"TNF-alpha"/-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. CONCLUSIONS: A /"TNF-alpha"/ SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study. | [
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16322490 | Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. | BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). TNF-alpha-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. CONCLUSIONS: A TNF-alpha SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study. | Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. | BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new /"intracranial hemorrhage"/ (/"ICH"/) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new /"ICH"/ after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: /"interleukin-6"/ (/"IL-6"/-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new /"ICH"/ was screened using chi2; SNPs associated with new /"ICH"/ were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with /"ICH"/). TNF-alpha-238G>A was associated with increased risk of new /"ICH"/ after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new /"ICH"/ was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new /"ICH"/. CONCLUSIONS: A TNF-alpha SNP was associated with increased risk of new /"ICH"/ in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of /"BAVM hemorrhage"/ merits further study. | [
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} | {
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"entity_id": "D020300",
"entity_type": "Disease",
"text_name": "ICH"
} | No |
16322490 | Tumor necrosis factor-alpha-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. | BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). TNF-alpha-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. CONCLUSIONS: A TNF-alpha SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study. | /"Tumor necrosis factor-alpha"/-238G>A promoter polymorphism is associated with increased risk of new hemorrhage in the natural course of patients with brain arteriovenous malformations. | BACKGROUND AND PURPOSE: Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new /"intracranial hemorrhage"/ (/"ICH"/) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. METHODS: Patients with BAVM were longitudinally followed. Primary outcome was new /"ICH"/ after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; /"IL-6-572G>C) and tumor necrosis factor-alpha"/ (/"TNF-alpha"/-238G>A; /"TNF-alpha"/-308G>A). Association of genotype with risk of new /"ICH"/ was screened using chi2; SNPs associated with new /"ICH"/ were further characterized using Cox proportional hazards. RESULTS: We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with /"ICH"/). /"TNF-alpha"/-238G>A was associated with increased risk of new /"ICH"/ after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new /"ICH"/ was increased for patients with /"TNF-alpha"/-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new /"ICH"/. CONCLUSIONS: A /"TNF-alpha"/ SNP was associated with increased risk of new /"ICH"/ in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of /"BAVM hemorrhage"/ merits further study. | [
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16324400 | [Mutational analysis of BRCA1 and BRCA2 genes in early-onset breast cancer patients in Shanghai]. | OBJECTIVE: To investigate the prevalence of BRCA1 and BRCA2 mutations among early-onset breast cancer patients in Shanghai. METHODS: Fifty patients unselected for family history, who were diagnosed with breast cancer before the age of 40 years were analyzed. Among them, 13 patients have at least one first-degree relative affected with breast cancer. Mutation screening of BRCA1 and BRCA2 was performed in the whole coding sequence through Denaturing High Performance Liquid Chromatography (DHPLC) and subsequent DNA direct sequencing. RESULTS: Six deleterious mutations, including 2 novel frameshift mutations (3449insA, 5587-1del8) and 2 novel splice-site mutations (IVS17-1G > T, IVS21 + 1G > C) in BRCA1 were identified. Two deleterious mutations detected in BRCA2, including one frameshift mutation (5950delCT) and one novel missense mutation (5911G > C), all occurring on exon 11 adjacently. Additional 12 novel sequence variants were also detected including one unclassified variant and 7 intronic variants in BRCA1, and 4 novel intronic variants in BRCA2, all causing no alteration of amino acid coding. The prevalence of BRCA1 and BRCA2 mutations in the patients with early-onset breast cancer was 12% and 4%, respectively. CONCLUSION: Four novel mutations in BRCA1 and one novel mutation in BRCA2 may be mutations characterized of early-onset breast cancer in Chinese population. Germline mutations in BRCA2 may contribute less than mutations in BRCA1 to early-onset breast cancer in Shanghai. These data contribute to information on spectrum of BRCA gene in Chinese population and also offer a recommended screening mode for clinical genetic testing programme in China. | [Mutational analysis of /"BRCA1"/ and BRCA2 genes in early-onset /"breast cancer"/ patients in Shanghai]. | OBJECTIVE: To investigate the prevalence of /"BRCA1"/ and BRCA2 mutations among early-onset /"breast cancer"/ patients in Shanghai. METHODS: Fifty patients unselected for family history, who were diagnosed with /"breast cancer"/ before the age of 40 years were analyzed. Among them, 13 patients have at least one first-degree relative affected with /"breast cancer"/. Mutation screening of /"BRCA1"/ and BRCA2 was performed in the whole coding sequence through Denaturing High Performance Liquid Chromatography (DHPLC) and subsequent DNA direct sequencing. RESULTS: Six deleterious mutations, including 2 novel frameshift mutations (3449insA, 5587-1del8) and 2 novel splice-site mutations (IVS17-1G > T, IVS21 + 1G > C) in /"BRCA1"/ were identified. Two deleterious mutations detected in BRCA2, including one frameshift mutation (5950delCT) and one novel missense mutation (5911G > C), all occurring on exon 11 adjacently. Additional 12 novel sequence variants were also detected including one unclassified variant and 7 intronic variants in /"BRCA1"/, and 4 novel intronic variants in BRCA2, all causing no alteration of amino acid coding. The prevalence of /"BRCA1"/ and BRCA2 mutations in the patients with early-onset /"breast cancer"/ was 12% and 4%, respectively. CONCLUSION: Four novel mutations in /"BRCA1"/ and one novel mutation in BRCA2 may be mutations characterized of early-onset /"breast cancer"/ in Chinese population. Germline mutations in BRCA2 may contribute less than mutations in /"BRCA1"/ to early-onset /"breast cancer"/ in Shanghai. These data contribute to information on spectrum of /"BRCA"/ gene in Chinese population and also offer a recommended screening mode for clinical genetic testing programme in China. | [
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16324400 | [Mutational analysis of BRCA1 and BRCA2 genes in early-onset breast cancer patients in Shanghai]. | OBJECTIVE: To investigate the prevalence of BRCA1 and BRCA2 mutations among early-onset breast cancer patients in Shanghai. METHODS: Fifty patients unselected for family history, who were diagnosed with breast cancer before the age of 40 years were analyzed. Among them, 13 patients have at least one first-degree relative affected with breast cancer. Mutation screening of BRCA1 and BRCA2 was performed in the whole coding sequence through Denaturing High Performance Liquid Chromatography (DHPLC) and subsequent DNA direct sequencing. RESULTS: Six deleterious mutations, including 2 novel frameshift mutations (3449insA, 5587-1del8) and 2 novel splice-site mutations (IVS17-1G > T, IVS21 + 1G > C) in BRCA1 were identified. Two deleterious mutations detected in BRCA2, including one frameshift mutation (5950delCT) and one novel missense mutation (5911G > C), all occurring on exon 11 adjacently. Additional 12 novel sequence variants were also detected including one unclassified variant and 7 intronic variants in BRCA1, and 4 novel intronic variants in BRCA2, all causing no alteration of amino acid coding. The prevalence of BRCA1 and BRCA2 mutations in the patients with early-onset breast cancer was 12% and 4%, respectively. CONCLUSION: Four novel mutations in BRCA1 and one novel mutation in BRCA2 may be mutations characterized of early-onset breast cancer in Chinese population. Germline mutations in BRCA2 may contribute less than mutations in BRCA1 to early-onset breast cancer in Shanghai. These data contribute to information on spectrum of BRCA gene in Chinese population and also offer a recommended screening mode for clinical genetic testing programme in China. | [Mutational analysis of BRCA1 and /"BRCA2"/ genes in early-onset /"breast cancer"/ patients in Shanghai]. | OBJECTIVE: To investigate the prevalence of BRCA1 and /"BRCA2"/ mutations among early-onset /"breast cancer"/ patients in Shanghai. METHODS: Fifty patients unselected for family history, who were diagnosed with /"breast cancer"/ before the age of 40 years were analyzed. Among them, 13 patients have at least one first-degree relative affected with /"breast cancer"/. Mutation screening of BRCA1 and /"BRCA2"/ was performed in the whole coding sequence through Denaturing High Performance Liquid Chromatography (DHPLC) and subsequent DNA direct sequencing. RESULTS: Six deleterious mutations, including 2 novel frameshift mutations (3449insA, 5587-1del8) and 2 novel splice-site mutations (IVS17-1G > T, IVS21 + 1G > C) in BRCA1 were identified. Two deleterious mutations detected in /"BRCA2"/, including one frameshift mutation (5950delCT) and one novel missense mutation (5911G > C), all occurring on exon 11 adjacently. Additional 12 novel sequence variants were also detected including one unclassified variant and 7 intronic variants in BRCA1, and 4 novel intronic variants in /"BRCA2"/, all causing no alteration of amino acid coding. The prevalence of BRCA1 and /"BRCA2"/ mutations in the patients with early-onset /"breast cancer"/ was 12% and 4%, respectively. CONCLUSION: Four novel mutations in BRCA1 and one novel mutation in /"BRCA2"/ may be mutations characterized of early-onset /"breast cancer"/ in Chinese population. Germline mutations in /"BRCA2"/ may contribute less than mutations in BRCA1 to early-onset /"breast cancer"/ in Shanghai. These data contribute to information on spectrum of BRCA gene in Chinese population and also offer a recommended screening mode for clinical genetic testing programme in China. | [
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16331614 | Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. | Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80%, and following the first diagnosis the 10-year risk of contralateral breast cancer is approximately 30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30-0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65). | Tamoxifen and /"contralateral breast cancer"/ in /"BRCA1"/ and BRCA2 carriers: an update. | Women with a mutation in /"BRCA1"/ or BRCA2 face a lifetime risk of /"breast cancer"/ of approximately 80%, and following the first diagnosis the 10-year risk of /"contralateral breast cancer"/ is approximately 30%. It has been shown that both tamoxifen and oophorectomy prevent /"contralateral breast cancer"/, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in /"BRCA1"/ and BRCA2 carriers has not been well evaluated. We studied 285 women with /"bilateral breast cancer"/ and a /"BRCA1"/ or BRCA2 mutation, and 751 control women with /"unilateral breast cancer"/ and a /"BRCA1"/ or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of /"breast cancer"/ and had been followed for as long as the case for a second primary /"breast cancer"/. The history of tamoxifen use for treating the first /"breast cancer"/ was compared between bilateral and unilateral cases. The multivariate odds ratio for /"contralateral breast cancer"/ associated with tamoxifen use was 0.50 for carriers of /"BRCA1"/ mutations (95% CI, 0.30-0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65). | [
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16331614 | Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. | Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80%, and following the first diagnosis the 10-year risk of contralateral breast cancer is approximately 30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30-0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65). | Tamoxifen and /"contralateral breast cancer"/ in BRCA1 and /"BRCA2"/ carriers: an update. | Women with a mutation in BRCA1 or /"BRCA2"/ face a lifetime risk of /"breast cancer"/ of approximately 80%, and following the first diagnosis the 10-year risk of /"contralateral breast cancer"/ is approximately 30%. It has been shown that both tamoxifen and oophorectomy prevent /"contralateral breast cancer"/, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and /"BRCA2"/ carriers has not been well evaluated. We studied 285 women with /"bilateral breast cancer"/ and a BRCA1 or /"BRCA2"/ mutation, and 751 control women with /"unilateral breast cancer"/ and a BRCA1 or /"BRCA2"/ mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of /"breast cancer"/ and had been followed for as long as the case for a second primary /"breast cancer"/. The history of tamoxifen use for treating the first /"breast cancer"/ was compared between bilateral and unilateral cases. The multivariate odds ratio for /"contralateral breast cancer"/ associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30-0.85) and was 0.42 for carriers of /"BRCA2"/ mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65). | [
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16344274 | ADH3 genotype, alcohol intake and breast cancer risk. | Moderate alcohol consumption of approximately 1-2 drinks per day has been associated with a 30-50% increase in breast cancer risk. Individuals differ in their ability to metabolize alcohol through genetic differences in alcohol dehydrogenase (ADH), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Individuals differ in their ADH genotype, and one locus in particular (ADH3) is polymorphic in Caucasian populations. Using data from the Long Island Breast Cancer Study Project, we examined whether fast metabolizers of alcohol, as measured by the ADH3(1-1) genotype, have a higher risk of breast cancer from alcohol intake compared with those individuals who are slow metabolizers, but consume similar amounts of alcohol. We combined genotyping information with questionnaire data on 1047 breast cancer cases and 1101 controls and used unconditional logistic regression methods to estimate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between alcohol intake and breast cancer risk. Among individuals homozygous for the fast metabolizing allele (ADH(3)1-1), a lifetime alcohol consumption of 15-30 g/day (approximately 1-2 drinks per day) increased breast cancer risk by 2-fold (OR=2.0, 95% CI=1.1-3.5). In contrast, the increase in risk from a lifetime alcohol consumption of 15-30 g/day was less pronounced in the intermediate and slow metabolizing groups, respectively: ADH3(1-2) (OR=1.5, 95% CI 0.9-2.4) and ADH(3)2-2 (OR=1.3, 95% CI 0.5-3.5). Fast metabolizers who drank 15-30 g/day of alcohol had 2.3 times (95% CI 1.3-4.0) greater risk of breast cancer than non-drinkers who were intermediate or slow metabolizers. This association for fast metabolizers who drank 15-30 g/day was particularly pronounced among premenopausal women (premenopausal women OR=2.9, 95 % CI=1.2-7.1; postmenopausal women OR=1.8, 95% CI=0.9-3.8). These population-based data support the hypothesis that fast metabolizers of alcohol have a higher risk of breast cancer risk, from alcohol intake than slow metabolizers. | /"ADH3"/ genotype, alcohol intake and /"breast cancer"/ risk. | Moderate alcohol consumption of approximately 1-2 drinks per day has been associated with a 30-50% increase in /"breast cancer"/ risk. Individuals differ in their ability to metabolize alcohol through genetic differences in alcohol dehydrogenase (ADH), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Individuals differ in their ADH genotype, and one locus in particular (/"ADH3"/) is polymorphic in Caucasian populations. Using data from the Long Island Breast Cancer Study Project, we examined whether fast metabolizers of alcohol, as measured by the /"ADH3"/(1-1) genotype, have a higher risk of /"breast cancer"/ from alcohol intake compared with those individuals who are slow metabolizers, but consume similar amounts of alcohol. We combined genotyping information with questionnaire data on 1047 /"breast cancer"/ cases and 1101 controls and used unconditional logistic regression methods to estimate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between alcohol intake and /"breast cancer"/ risk. Among individuals homozygous for the fast metabolizing allele (ADH(3)1-1), a lifetime alcohol consumption of 15-30 g/day (approximately 1-2 drinks per day) increased /"breast cancer"/ risk by 2-fold (OR=2.0, 95% CI=1.1-3.5). In contrast, the increase in risk from a lifetime alcohol consumption of 15-30 g/day was less pronounced in the intermediate and slow metabolizing groups, respectively: /"ADH3"/(1-2) (OR=1.5, 95% CI 0.9-2.4) and ADH(3)2-2 (OR=1.3, 95% CI 0.5-3.5). Fast metabolizers who drank 15-30 g/day of alcohol had 2.3 times (95% CI 1.3-4.0) greater risk of /"breast cancer"/ than non-drinkers who were intermediate or slow metabolizers. This association for fast metabolizers who drank 15-30 g/day was particularly pronounced among premenopausal women (premenopausal women OR=2.9, 95 % CI=1.2-7.1; postmenopausal women OR=1.8, 95% CI=0.9-3.8). These population-based data support the hypothesis that fast metabolizers of alcohol have a higher risk of /"breast cancer"/ risk, from alcohol intake than slow metabolizers. | [
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16344274 | ADH3 genotype, alcohol intake and breast cancer risk. | Moderate alcohol consumption of approximately 1-2 drinks per day has been associated with a 30-50% increase in breast cancer risk. Individuals differ in their ability to metabolize alcohol through genetic differences in alcohol dehydrogenase (ADH), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Individuals differ in their ADH genotype, and one locus in particular (ADH3) is polymorphic in Caucasian populations. Using data from the Long Island Breast Cancer Study Project, we examined whether fast metabolizers of alcohol, as measured by the ADH3(1-1) genotype, have a higher risk of breast cancer from alcohol intake compared with those individuals who are slow metabolizers, but consume similar amounts of alcohol. We combined genotyping information with questionnaire data on 1047 breast cancer cases and 1101 controls and used unconditional logistic regression methods to estimate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between alcohol intake and breast cancer risk. Among individuals homozygous for the fast metabolizing allele (ADH(3)1-1), a lifetime alcohol consumption of 15-30 g/day (approximately 1-2 drinks per day) increased breast cancer risk by 2-fold (OR=2.0, 95% CI=1.1-3.5). In contrast, the increase in risk from a lifetime alcohol consumption of 15-30 g/day was less pronounced in the intermediate and slow metabolizing groups, respectively: ADH3(1-2) (OR=1.5, 95% CI 0.9-2.4) and ADH(3)2-2 (OR=1.3, 95% CI 0.5-3.5). Fast metabolizers who drank 15-30 g/day of alcohol had 2.3 times (95% CI 1.3-4.0) greater risk of breast cancer than non-drinkers who were intermediate or slow metabolizers. This association for fast metabolizers who drank 15-30 g/day was particularly pronounced among premenopausal women (premenopausal women OR=2.9, 95 % CI=1.2-7.1; postmenopausal women OR=1.8, 95% CI=0.9-3.8). These population-based data support the hypothesis that fast metabolizers of alcohol have a higher risk of breast cancer risk, from alcohol intake than slow metabolizers. | /"ADH3"/ genotype, alcohol intake and breast cancer risk. | Moderate alcohol consumption of approximately 1-2 drinks per day has been associated with a 30-50% increase in breast cancer risk. Individuals differ in their ability to metabolize alcohol through genetic differences in /"alcohol dehydrogenase"/ (/"ADH"/), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Individuals differ in their /"ADH"/ genotype, and one locus in particular (/"ADH3"/) is polymorphic in Caucasian populations. Using data from the Long Island Breast Cancer Study Project, we examined whether fast metabolizers of alcohol, as measured by the /"ADH3"/(1-1) genotype, have a higher risk of breast cancer from alcohol intake compared with those individuals who are slow metabolizers, but consume similar amounts of alcohol. We combined genotyping information with questionnaire data on 1047 breast cancer cases and 1101 controls and used unconditional logistic regression methods to estimate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between alcohol intake and breast cancer risk. Among individuals homozygous for the fast metabolizing allele (/"ADH"/(3)1-1), a lifetime alcohol consumption of 15-30 g/day (approximately 1-2 drinks per day) increased breast cancer risk by 2-fold (OR=2.0, 95% CI=1.1-3.5). In contrast, the increase in risk from a lifetime alcohol consumption of 15-30 g/day was less pronounced in the intermediate and slow metabolizing groups, respectively: /"ADH3"/(1-2) (OR=1.5, 95% CI 0.9-2.4) and /"ADH"/(3)2-2 (OR=1.3, 95% CI 0.5-3.5). Fast metabolizers who drank 15-30 g/day of alcohol had 2.3 times (95% CI 1.3-4.0) greater risk of breast cancer than non-drinkers who were intermediate or slow metabolizers. This association for fast metabolizers who drank 15-30 g/day was particularly pronounced among premenopausal women (premenopausal women OR=2.9, 95 % CI=1.2-7.1; postmenopausal women OR=1.8, 95% CI=0.9-3.8). These population-based data support the hypothesis that fast metabolizers of alcohol have a higher risk of breast cancer risk, from alcohol intake than slow metabolizers. | [
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16352452 | Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification. | A DNA-proven Tay-Sachs disease (TSD) carrier and his brother were found to have serum percent Hexosaminidase A (%HexA) enzymatic activities in the non-carrier range, while the leukocyte %HexA profiles clearly identified them as TSD heterozygotes. Both their serum HexA and HexB enzymatic activities were below reference range, suggesting inheritance of mutations in both the HEXA (alpha-subunit) and HEXB (beta-subunit) genes. DNA sequencing revealed that both individuals, carried the common HEXA 1277_1278insTATC mutation, and two common HEXB polymorphisms: [619A>G (+) delTG]. To determine if these HEXB polymorphisms reduce HexA and HexB enzymatic activities, 69 DNA samples from subjects previously screened enzymatically in both serum and leukocytes for TSD carrier status were selected for either high, mid-range or low serum Total Hex (defined as the sum of HexA and HexB) activities and were tested for the HEXB mutations. Further, three additional TSD carriers ascertained by the atypical pattern of normal serum %HexA but carrier leukocyte %HexA, were found to have the [delTG (+) 619A>G] genotype. In addition, the frequency of the [delTG (+) 619A>G] genotype was significantly higher (P < 0.01) in subjects with low serum HexB enzymatic activities. Given the high frequency of the [delTG (+) 619A>G] haplotype in the Ashkenazi Jewish population (approximately 10%), up to 10% of TSD carriers may have normal serum %HexA values with low total Hex. Accordingly, serum %HexA should not be the sole criterion used for carrier status determination. Where total Hex activity is reduced, further testing with leukocyte Hex profiles is indicated. | Common /"HEXB"/ polymorphisms reduce serum HexA and /"HexB"/ enzymatic activities, potentially masking /"Tay-Sachs disease"/ carrier identification. | A DNA-proven /"Tay-Sachs disease"/ (/"TSD"/) carrier and his brother were found to have serum percent Hexosaminidase A (%HexA) enzymatic activities in the non-carrier range, while the leukocyte %HexA profiles clearly identified them as /"TSD"/ heterozygotes. Both their serum HexA and /"HexB"/ enzymatic activities were below reference range, suggesting inheritance of mutations in both the HEXA (/"alpha-subunit) and HEXB"/ (beta-subunit) genes. DNA sequencing revealed that both individuals, carried the common HEXA 1277_1278insTATC mutation, and two common /"HEXB"/ polymorphisms: [619A>G (+) delTG]. To determine if these /"HEXB"/ polymorphisms reduce HexA and /"HexB"/ enzymatic activities, 69 DNA samples from subjects previously screened enzymatically in both serum and leukocytes for /"TSD"/ carrier status were selected for either high, mid-range or low serum Total /"Hex"/ (defined as the sum of HexA and /"HexB"/) activities and were tested for the /"HEXB"/ mutations. Further, three additional /"TSD"/ carriers ascertained by the atypical pattern of normal serum %HexA but carrier leukocyte %HexA, were found to have the [delTG (+) 619A>G] genotype. In addition, the frequency of the [delTG (+) 619A>G] genotype was significantly higher (P < 0.01) in subjects with low serum /"HexB"/ enzymatic activities. Given the high frequency of the [delTG (+) 619A>G] haplotype in the Ashkenazi Jewish population (approximately 10%), up to 10% of /"TSD"/ carriers may have normal serum %HexA values with low total /"Hex"/. Accordingly, serum %HexA should not be the sole criterion used for carrier status determination. Where total /"Hex"/ activity is reduced, further testing with leukocyte /"Hex"/ profiles is indicated. | [
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} | Yes |
16352452 | Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification. | A DNA-proven Tay-Sachs disease (TSD) carrier and his brother were found to have serum percent Hexosaminidase A (%HexA) enzymatic activities in the non-carrier range, while the leukocyte %HexA profiles clearly identified them as TSD heterozygotes. Both their serum HexA and HexB enzymatic activities were below reference range, suggesting inheritance of mutations in both the HEXA (alpha-subunit) and HEXB (beta-subunit) genes. DNA sequencing revealed that both individuals, carried the common HEXA 1277_1278insTATC mutation, and two common HEXB polymorphisms: [619A>G (+) delTG]. To determine if these HEXB polymorphisms reduce HexA and HexB enzymatic activities, 69 DNA samples from subjects previously screened enzymatically in both serum and leukocytes for TSD carrier status were selected for either high, mid-range or low serum Total Hex (defined as the sum of HexA and HexB) activities and were tested for the HEXB mutations. Further, three additional TSD carriers ascertained by the atypical pattern of normal serum %HexA but carrier leukocyte %HexA, were found to have the [delTG (+) 619A>G] genotype. In addition, the frequency of the [delTG (+) 619A>G] genotype was significantly higher (P < 0.01) in subjects with low serum HexB enzymatic activities. Given the high frequency of the [delTG (+) 619A>G] haplotype in the Ashkenazi Jewish population (approximately 10%), up to 10% of TSD carriers may have normal serum %HexA values with low total Hex. Accordingly, serum %HexA should not be the sole criterion used for carrier status determination. Where total Hex activity is reduced, further testing with leukocyte Hex profiles is indicated. | Common HEXB polymorphisms reduce serum /"HexA"/ and HexB enzymatic activities, potentially masking /"Tay-Sachs disease"/ carrier identification. | A DNA-proven /"Tay-Sachs disease"/ (/"TSD"/) carrier and his brother were found to have serum percent Hexosaminidase A (%/"HexA"/) enzymatic activities in the non-carrier range, while the leukocyte %/"HexA"/ profiles clearly identified them as /"TSD"/ heterozygotes. Both their serum /"HexA"/ and HexB enzymatic activities were below reference range, suggesting inheritance of mutations in both the /"HEXA"/ (alpha-subunit) and HEXB (beta-subunit) genes. DNA sequencing revealed that both individuals, carried the common /"HEXA"/ 1277_1278insTATC mutation, and two common HEXB polymorphisms: [619A>G (+) delTG]. To determine if these HEXB polymorphisms reduce /"HexA"/ and HexB enzymatic activities, 69 DNA samples from subjects previously screened enzymatically in both serum and leukocytes for /"TSD"/ carrier status were selected for either high, mid-range or low serum Total Hex (defined as the sum of /"HexA"/ and HexB) activities and were tested for the HEXB mutations. Further, three additional /"TSD"/ carriers ascertained by the atypical pattern of normal serum %/"HexA"/ but carrier leukocyte %/"HexA"/, were found to have the [delTG (+) 619A>G] genotype. In addition, the frequency of the [delTG (+) 619A>G] genotype was significantly higher (P < 0.01) in subjects with low serum HexB enzymatic activities. Given the high frequency of the [delTG (+) 619A>G] haplotype in the Ashkenazi Jewish population (approximately 10%), up to 10% of /"TSD"/ carriers may have normal serum %/"HexA"/ values with low total Hex. Accordingly, serum %/"HexA"/ should not be the sole criterion used for carrier status determination. Where total Hex activity is reduced, further testing with leukocyte Hex profiles is indicated. | [
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} | {
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"entity_id": "D013661",
"entity_type": "Disease",
"text_name": "TSD"
} | No |
16352477 | Meesmann corneal dystrophy (MECD): report of 2 families and a novel mutation in the cornea specific keratin 12 (KRT12) gene. | PURPOSE: Meesmann corneal dystrophy (MECD) is an autosomal dominant disorder affecting the corneal epithelium. It is caused by heterozygous mutations in KRT3 or KRT12 gene. Actually, 14 mutations have been reported, 1 in KRT3 and 13 in KRT12. These genes were screened in several patients suffering from MECD. METHODS: Patients from 2 families were screened for mutation in KRT3 and KRT12. Exons were PCR-amplified and directly sequenced. The new mutation was checked by DHPLC in 51 control individuals of Swiss origin. RESULTS/CONCLUSIONS: In one family, the M129T heterozygous mutation was observed in KRT12. In the second family, we identified a novel I426S heterozygous mutation in exon 6 of KRT12. | /"Meesmann corneal dystrophy"/ (/"MECD"/): report of 2 families and a novel mutation in the cornea specific /"keratin 12"/ (/"KRT12"/) gene. | PURPOSE: /"Meesmann corneal dystrophy"/ (/"MECD"/) is an autosomal dominant disorder affecting the corneal epithelium. It is caused by heterozygous mutations in KRT3 or /"KRT12"/ gene. Actually, 14 mutations have been reported, 1 in KRT3 and 13 in /"KRT12"/. These genes were screened in several patients suffering from /"MECD"/. METHODS: Patients from 2 families were screened for mutation in KRT3 and /"KRT12"/. Exons were PCR-amplified and directly sequenced. The new mutation was checked by DHPLC in 51 control individuals of Swiss origin. RESULTS/CONCLUSIONS: In one family, the M129T heterozygous mutation was observed in /"KRT12"/. In the second family, we identified a novel I426S heterozygous mutation in exon 6 of /"KRT12"/. | [
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"entity_type": "Disease",
"text_name": "autosomal dominant disorder"
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] | {
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"text_name": "keratin 12"
} | {
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"entity_id": "D053559",
"entity_type": "Disease",
"text_name": "Meesmann corneal dystrophy"
} | Yes |
16352477 | Meesmann corneal dystrophy (MECD): report of 2 families and a novel mutation in the cornea specific keratin 12 (KRT12) gene. | PURPOSE: Meesmann corneal dystrophy (MECD) is an autosomal dominant disorder affecting the corneal epithelium. It is caused by heterozygous mutations in KRT3 or KRT12 gene. Actually, 14 mutations have been reported, 1 in KRT3 and 13 in KRT12. These genes were screened in several patients suffering from MECD. METHODS: Patients from 2 families were screened for mutation in KRT3 and KRT12. Exons were PCR-amplified and directly sequenced. The new mutation was checked by DHPLC in 51 control individuals of Swiss origin. RESULTS/CONCLUSIONS: In one family, the M129T heterozygous mutation was observed in KRT12. In the second family, we identified a novel I426S heterozygous mutation in exon 6 of KRT12. | Meesmann corneal dystrophy (MECD): report of 2 families and a novel mutation in the cornea specific /"keratin 12"/ (/"KRT12"/) gene. | PURPOSE: Meesmann corneal dystrophy (MECD) is an /"autosomal dominant disorder"/ affecting the corneal epithelium. It is caused by heterozygous mutations in KRT3 or /"KRT12"/ gene. Actually, 14 mutations have been reported, 1 in KRT3 and 13 in /"KRT12"/. These genes were screened in several patients suffering from MECD. METHODS: Patients from 2 families were screened for mutation in KRT3 and /"KRT12"/. Exons were PCR-amplified and directly sequenced. The new mutation was checked by DHPLC in 51 control individuals of Swiss origin. RESULTS/CONCLUSIONS: In one family, the M129T heterozygous mutation was observed in /"KRT12"/. In the second family, we identified a novel I426S heterozygous mutation in exon 6 of /"KRT12"/. | [
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} | {
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"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal dominant disorder"
} | No |
16358723 | [Comparison CCR5de132 mutation in the CCR5 gene frequencies in Russians, Tuvinians, and in different groups of HIV-infected individuals]. | The 32-bp deletion (CCR5del32 mutation) in the CCR5 (chemokine (C-C motif) receptor 5) gene, encoding CCR5 chemokine receptor, is one of the factors determining natural resistance to human immunodeficiency virus (HIV-1) infection. In the present study, the samples of Russians (n = 107), Tuvinians (n = 50), and HIV-infected individuals were examined for the presence of CCR5del32 mutation in the CCR5 gene. The CCR5del32 allele frequency in Russians and Tuvinians constituted 7.84 and 2%, respectively. Among HIV-1 infected individuals, two groups, of macrophage-tropic HIV-1 strain- and T-cell-tropic HIV-1 strain-infected were distinguished. The CCR5del32 allele frequency in the first group (6.45%) was lower than in the second one (8.73%). Statistical treatment of the HIV-1 infected individuals typing data showed that the difference in the CCR5del32 allele frequencies between the groups of sexually (macrophage-tropic) and parenterally (T-cell-tropic) infected individuals observed was within the limit of random deviation. | [Comparison CCR5de132 mutation in the /"CCR5"/ gene frequencies in Russians, Tuvinians, and in different groups of /"HIV-infected"/ individuals]. | The 32-bp deletion (CCR5del32 mutation) in the /"CCR5"/ (chemokine (C-C motif) receptor 5) gene, encoding /"CCR5"/ chemokine receptor, is one of the factors determining natural resistance to /"human immunodeficiency virus (HIV-1) infection"/. In the present study, the samples of Russians (n = 107), Tuvinians (n = 50), and /"HIV-infected"/ individuals were examined for the presence of CCR5del32 mutation in the /"CCR5"/ gene. The /"CCR5"/del32 allele frequency in Russians and Tuvinians constituted 7.84 and 2%, respectively. Among /"HIV-1 infected"/ individuals, two groups, of macrophage-tropic HIV-1 strain- and /"T-cell-tropic HIV-1 strain-infected"/ were distinguished. The /"CCR5"/del32 allele frequency in the first group (6.45%) was lower than in the second one (8.73%). Statistical treatment of the /"HIV-1 infected"/ individuals typing data showed that the difference in the CCR5del32 allele frequencies between the groups of sexually (macrophage-tropic) and parenterally (T-cell-tropic) infected individuals observed was within the limit of random deviation. | [
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"entity_id": "D015658",
"entity_type": "Disease",
"text_name": "human immunodeficiency virus (HIV-1) infection"
} | Yes |
16359492 | Comprehensive screening of CREB-binding protein gene mutations among patients with Rubinstein-Taybi syndrome using denaturing high-performance liquid chromatography. | Mutations in the CREBBP (CREB-binding protein gene) cause Rubinstein-Taybi syndrome (RSTS). At present, however, genetic testing of CREBBP is not commonly applied in clinical settings because the currently available assays are technically and financially demanding, mainly because of the size of the gene. In the present study, we took advantage of a highly sensitive and specific, automated denaturing high-performance liquid chromatography (DHPLC) technique. First, we developed a DHPLC-based protocol to analyze the entire coding region of CREBBP. Second, we analyzed genetic samples from 21 RSTS patients using DHPLC. The coding region was amplified by 41 primer pairs, all of which have the same cycling conditions, aliquoted on a 96-well format PCR plate. In this manner, all the exons were simultaneously amplified using a single block in a PCR machine. We then wrote a computer script to analyze all the PCR amplicons generated from various portions of the CREBBP gene in a serial manner at optimized conditions determined individually for each amplicon. Heterozygous CREBBP mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice-site mutations, and two missense mutations. The resulting detection rate of 57% was comparable to the outcome of previous studies. The relatively high detection rate in the present study demonstrates the enhanced sensitivity of the DHPLC-based mutation analysis, as exemplified by mutation analyses of other genes. The implementation of similar methodologies for other dysmorphic syndromes will help medical geneticists to confirm their clinical impressions and to provide accurate genetic counseling for patients and their families. | Comprehensive screening of /"CREB-binding protein"/ gene mutations among patients with /"Rubinstein-Taybi syndrome"/ using denaturing high-performance liquid chromatography. | Mutations in the /"CREBBP"/ (/"CREB-binding protein gene"/) cause /"Rubinstein-Taybi syndrome"/ (/"RSTS"/). At present, however, genetic testing of /"CREBBP"/ is not commonly applied in clinical settings because the currently available assays are technically and financially demanding, mainly because of the size of the gene. In the present study, we took advantage of a highly sensitive and specific, automated denaturing high-performance liquid chromatography (DHPLC) technique. First, we developed a DHPLC-based protocol to analyze the entire coding region of /"CREBBP"/. Second, we analyzed genetic samples from 21 /"RSTS"/ patients using DHPLC. The coding region was amplified by 41 primer pairs, all of which have the same cycling conditions, aliquoted on a 96-well format PCR plate. In this manner, all the exons were simultaneously amplified using a single block in a PCR machine. We then wrote a computer script to analyze all the PCR amplicons generated from various portions of the /"CREBBP"/ gene in a serial manner at optimized conditions determined individually for each amplicon. Heterozygous /"CREBBP"/ mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice-site mutations, and two missense mutations. The resulting detection rate of 57% was comparable to the outcome of previous studies. The relatively high detection rate in the present study demonstrates the enhanced sensitivity of the DHPLC-based mutation analysis, as exemplified by mutation analyses of other genes. The implementation of similar methodologies for other dysmorphic syndromes will help medical geneticists to confirm their clinical impressions and to provide accurate genetic counseling for patients and their families. | [
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16359492 | Comprehensive screening of CREB-binding protein gene mutations among patients with Rubinstein-Taybi syndrome using denaturing high-performance liquid chromatography. | Mutations in the CREBBP (CREB-binding protein gene) cause Rubinstein-Taybi syndrome (RSTS). At present, however, genetic testing of CREBBP is not commonly applied in clinical settings because the currently available assays are technically and financially demanding, mainly because of the size of the gene. In the present study, we took advantage of a highly sensitive and specific, automated denaturing high-performance liquid chromatography (DHPLC) technique. First, we developed a DHPLC-based protocol to analyze the entire coding region of CREBBP. Second, we analyzed genetic samples from 21 RSTS patients using DHPLC. The coding region was amplified by 41 primer pairs, all of which have the same cycling conditions, aliquoted on a 96-well format PCR plate. In this manner, all the exons were simultaneously amplified using a single block in a PCR machine. We then wrote a computer script to analyze all the PCR amplicons generated from various portions of the CREBBP gene in a serial manner at optimized conditions determined individually for each amplicon. Heterozygous CREBBP mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice-site mutations, and two missense mutations. The resulting detection rate of 57% was comparable to the outcome of previous studies. The relatively high detection rate in the present study demonstrates the enhanced sensitivity of the DHPLC-based mutation analysis, as exemplified by mutation analyses of other genes. The implementation of similar methodologies for other dysmorphic syndromes will help medical geneticists to confirm their clinical impressions and to provide accurate genetic counseling for patients and their families. | Comprehensive screening of /"CREB-binding protein"/ gene mutations among patients with Rubinstein-Taybi syndrome using denaturing high-performance liquid chromatography. | Mutations in the /"CREBBP"/ (/"CREB-binding protein gene"/) cause Rubinstein-Taybi syndrome (RSTS). At present, however, genetic testing of /"CREBBP"/ is not commonly applied in clinical settings because the currently available assays are technically and financially demanding, mainly because of the size of the gene. In the present study, we took advantage of a highly sensitive and specific, automated denaturing high-performance liquid chromatography (DHPLC) technique. First, we developed a DHPLC-based protocol to analyze the entire coding region of /"CREBBP"/. Second, we analyzed genetic samples from 21 RSTS patients using DHPLC. The coding region was amplified by 41 primer pairs, all of which have the same cycling conditions, aliquoted on a 96-well format PCR plate. In this manner, all the exons were simultaneously amplified using a single block in a PCR machine. We then wrote a computer script to analyze all the PCR amplicons generated from various portions of the /"CREBBP"/ gene in a serial manner at optimized conditions determined individually for each amplicon. Heterozygous /"CREBBP"/ mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice-site mutations, and two missense mutations. The resulting detection rate of 57% was comparable to the outcome of previous studies. The relatively high detection rate in the present study demonstrates the enhanced sensitivity of the DHPLC-based mutation analysis, as exemplified by mutation analyses of other genes. The implementation of similar methodologies for other /"dysmorphic syndromes"/ will help medical geneticists to confirm their clinical impressions and to provide accurate genetic counseling for patients and their families. | [
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16361275 | Replication of association of IL1 gene complex members with ankylosing spondylitis in Taiwanese Chinese. | OBJECTIVE: To test the association of interleukin 1 (IL1) gene family members with ankylosing spondylitis (AS), previously reported in Europid subjects, in an ethnically remote population. METHODS: 200 Taiwanese Chinese AS patients and 200 ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (SNPs) and the IL1RN.VNTR, markers previously associated with AS. Allele, genotype, and haplotype frequencies were compared between cases and controls. RESULTS: Association of alleles and genotypes of the markers IL1F10.3, IL1RN.4, and IL1RN.VNTR was observed with AS (p<0.05). Haplotypes of pairs of these markers and of the markers IL1RN.6/1 and IL1RN.6/2 were also significantly associated with AS. The strongest associations observed were with the marker IL1RN.4, and with the two-marker haplotype IL1RN.4-IL1RN.VNTR (both p = 0.004). Strong linkage disequilibrium was observed between all marker pairs except those involving IL1B-511 (D' 0.4 to 0.9, p<0.01). CONCLUSIONS: The IL1 gene cluster is associated with AS in Taiwanese Chinese. This finding provides strong statistical support that the previously observed association of this gene cluster with AS is a true positive finding. These authors contributed equally to the study. | Replication of association of IL1 gene complex members with /"ankylosing spondylitis"/ in Taiwanese Chinese. | OBJECTIVE: To test the association of interleukin 1 (IL1) gene family members with /"ankylosing spondylitis"/ (/"AS"/), previously reported in Europid subjects, in an ethnically remote population. METHODS: 200 Taiwanese Chinese /"AS"/ patients and 200 ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (SNPs) and the IL1RN.VNTR, markers previously associated with /"AS"/. Allele, genotype, and haplotype frequencies were compared between cases and controls. RESULTS: Association of alleles and genotypes of the markers /"IL1F10"/.3, IL1RN.4, and IL1RN.VNTR was observed with /"AS"/ (p<0.05). Haplotypes of pairs of these markers and of the markers IL1RN.6/1 and IL1RN.6/2 were also significantly associated with /"AS"/. The strongest associations observed were with the marker IL1RN.4, and with the two-marker haplotype IL1RN.4-IL1RN.VNTR (both p = 0.004). Strong linkage disequilibrium was observed between all marker pairs except those involving IL1B-511 (D' 0.4 to 0.9, p<0.01). CONCLUSIONS: The IL1 gene cluster is associated with /"AS"/ in Taiwanese Chinese. This finding provides strong statistical support that the previously observed association of this gene cluster with /"AS"/ is a true positive finding. These authors contributed equally to the study. | [
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