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19235789 | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in /"Alzheimer's disease"/. | OBJECTIVE: /"Alzheimer's disease"/ (/"AD"/) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in /"AD"/ has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, /"DRD3"/ and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable /"AD"/ patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), /"DRD3"/ (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between /"DRD3"/ and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in /"AD"/ patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | [
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19235789 | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, /"DRD2"/, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), /"DRD2"/ (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, /"hallucinations"/, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | [
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19235789 | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, /"DRD2"/, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (/"Neuropsychiatric"/ Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), /"DRD2"/ (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation//"aggression"/ and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | [
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"text_name": "aggression"
} | No |
19235789 | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from /"behavioural and psychological symptoms of dementia"/ (/"BPSD"/). A genetic component to the development of /"BPSD"/ in AD has been supported. Polymorphisms within dopamine receptors /"DRD1"/, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the /"BPSD"/ (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the /"DRD1"/ (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | [
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} | No |
19235789 | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from /"behavioural and psychological symptoms of dementia"/ (/"BPSD"/). A genetic component to the development of /"BPSD"/ in AD has been supported. Polymorphisms within dopamine receptors /"DRD1"/, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the /"BPSD"/ (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the /"DRD1"/ (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | [
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19237575 | The role of the CD58 locus in multiple sclerosis. | Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the CD58 gene region, encoding the costimulatory molecule LFA-3, are associated with risk of developing MS. We now report additional genetic evidence, as well as resequencing and fine mapping of the CD58 locus in patients with MS and control subjects. These efforts identify a CD58 variant that provides further evidence of association with MS (P = 1.1 x 10(-6), OR 0.82) and the single protective effect within the CD58 locus is captured by the rs2300747(G) allele. This protective rs2300747(G) allele is associated with a dose-dependent increase in CD58 mRNA expression in lymphoblastic cell lines (P = 1.1 x 10(-10)) and in peripheral blood mononuclear cells from MS subjects (P = 0.0037). This protective effect of enhanced CD58 expression on circulating mononuclear cells in patients with MS is supported by finding that CD58 mRNA expression is higher in MS subjects during clinical remission. Functional investigations suggest a potential mechanism whereby increases in CD58 expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of CD4(+)CD25(high) regulatory T cells that are defective in subjects with MS. | The role of the /"CD58"/ locus in /"multiple sclerosis"/. | /"Multiple sclerosis"/ (/"MS"/) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the /"CD58"/ gene region, encoding the costimulatory molecule /"LFA-3"/, are associated with risk of developing /"MS"/. We now report additional genetic evidence, as well as resequencing and fine mapping of the /"CD58"/ locus in patients with /"MS"/ and control subjects. These efforts identify a /"CD58"/ variant that provides further evidence of association with /"MS"/ (P = 1.1 x 10(-6), OR 0.82) and the single protective effect within the /"CD58"/ locus is captured by the rs2300747(G) allele. This protective rs2300747(G) allele is associated with a dose-dependent increase in /"CD58"/ mRNA expression in lymphoblastic cell lines (P = 1.1 x 10(-10)) and in peripheral blood mononuclear cells from /"MS"/ subjects (P = 0.0037). This protective effect of enhanced /"CD58"/ expression on circulating mononuclear cells in patients with /"MS"/ is supported by finding that /"CD58"/ mRNA expression is higher in /"MS"/ subjects during clinical remission. Functional investigations suggest a potential mechanism whereby increases in /"CD58"/ expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the /"CD58"/ receptor, CD2, leading to the enhanced function of CD4(+)CD25(high) regulatory T cells that are defective in subjects with /"MS"/. | [
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"text_name": "multiple sclerosis"
} | Yes |
19237575 | The role of the CD58 locus in multiple sclerosis. | Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the CD58 gene region, encoding the costimulatory molecule LFA-3, are associated with risk of developing MS. We now report additional genetic evidence, as well as resequencing and fine mapping of the CD58 locus in patients with MS and control subjects. These efforts identify a CD58 variant that provides further evidence of association with MS (P = 1.1 x 10(-6), OR 0.82) and the single protective effect within the CD58 locus is captured by the rs2300747(G) allele. This protective rs2300747(G) allele is associated with a dose-dependent increase in CD58 mRNA expression in lymphoblastic cell lines (P = 1.1 x 10(-10)) and in peripheral blood mononuclear cells from MS subjects (P = 0.0037). This protective effect of enhanced CD58 expression on circulating mononuclear cells in patients with MS is supported by finding that CD58 mRNA expression is higher in MS subjects during clinical remission. Functional investigations suggest a potential mechanism whereby increases in CD58 expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of CD4(+)CD25(high) regulatory T cells that are defective in subjects with MS. | The role of the /"CD58"/ locus in multiple sclerosis. | Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with /"demyelination"/ and axonal loss. A whole genome association scan suggested that allelic variants in the /"CD58"/ gene region, encoding the costimulatory molecule /"LFA-3"/, are associated with risk of developing MS. We now report additional genetic evidence, as well as resequencing and fine mapping of the /"CD58"/ locus in patients with MS and control subjects. These efforts identify a /"CD58"/ variant that provides further evidence of association with MS (P = 1.1 x 10(-6), OR 0.82) and the single protective effect within the /"CD58"/ locus is captured by the rs2300747(G) allele. This protective rs2300747(G) allele is associated with a dose-dependent increase in /"CD58"/ mRNA expression in lymphoblastic cell lines (P = 1.1 x 10(-10)) and in peripheral blood mononuclear cells from MS subjects (P = 0.0037). This protective effect of enhanced /"CD58"/ expression on circulating mononuclear cells in patients with MS is supported by finding that /"CD58"/ mRNA expression is higher in MS subjects during clinical remission. Functional investigations suggest a potential mechanism whereby increases in /"CD58"/ expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the /"CD58"/ receptor, CD2, leading to the enhanced function of CD4(+)CD25(high) regulatory T cells that are defective in subjects with MS. | [
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"text_name": "demyelination"
} | No |
19262484 | Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. | Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop hypertension. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of alcoholism. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for ADH1B Arg47His (rs1229984) and ALDH2 Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population. | Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. | Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop hypertension. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of /"alcoholism"/. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for ADH1B Arg47His (rs1229984) and /"ALDH2"/ Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population. | [
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"entity_type": "Disease",
"text_name": "alcoholism"
} | Yes |
19262484 | Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. | Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop hypertension. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of alcoholism. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for ADH1B Arg47His (rs1229984) and ALDH2 Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population. | Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. | Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop hypertension. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of /"alcoholism"/. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for /"ADH1B"/ Arg47His (rs1229984) and ALDH2 Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population. | [
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"entity_id": "D000437",
"entity_type": "Disease",
"text_name": "alcoholism"
} | Yes |
19262484 | Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. | Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop hypertension. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of alcoholism. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for ADH1B Arg47His (rs1229984) and ALDH2 Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population. | Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. | Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop /"hypertension"/. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of alcoholism. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for ADH1B Arg47His (rs1229984) and /"ALDH2"/ Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population. | [
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"text_name": "hypertension"
} | No |
19262484 | Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. | Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop hypertension. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of alcoholism. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for ADH1B Arg47His (rs1229984) and ALDH2 Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population. | Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. | Epidemiological studies have shown that excessive alcohol consumption is a potent risk factor to develop /"hypertension"/. In addition, some polymorphisms of the alcohol metabolism genes have been reported to exert significant impacts on the risk of alcoholism. We investigate the relevance of genetic susceptibility to drinking behavior and its influence on the sensitivity to pressor effects of alcohol in the Japanese general population. We initially screened SNPs in four candidate genes by resequencing. From 35 SNPs thus identified, 10 tag SNPs were selected and used for large-scale association analysis in a total of 5724 subjects. Among the SNPs tested, significant association (P<0.001) with drinking behavior was observed for /"ADH1B"/ Arg47His (rs1229984) and ALDH2 Glu487Lys (rs671) polymorphisms. All subjects with Lys homozygote (AA genotype) of rs671 turned out to be nondrinkers and the combination of two SNP genotypes appeared to substantially influence people's drinking behavior in a synergistic manner. rs671 was significantly associated with blood pressure (P=0.0001-0.0491) in subgroups of drinkers. In the context of gene-environment interaction, our data clearly show the genetic impacts of two SNPs on drinking behavior and of one SNP on the sensitivity to the pressor effects of alcohol in the Japanese general population. | [
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} | No |
19262575 | Polymorphisms in the interleukin 3 gene show strong association with susceptibility to Graves' disease in Chinese population. | Graves' disease (GD) is a common organ-specific autoimmune disorder, which is multifactorial and develops in genetically susceptible individuals. We had earlier mapped a susceptibility locus for GD to chromosome 5q31-33 in a linkage study. Here we used tag single-nucleotide polymorphisms (SNPs) to search for genetic variants associated with GD, and examined 19 functional candidate genes in this chromosomal region. We identified 192 polymorphisms by re-sequencing the candidate genes, and selected 51 tagSNPs to genotype in a case-control collection of 1118 south Han Chinese subjects (428 cases and 690 controls). Initial analysis suggested that a non-synonymous SNP rs40401 (P27S) of interleukin 3 (IL3) was associated with GD, and further fine-mapping showed that rs40401, or its perfect proxy SNP rs31480 in the 5' flanking region of IL3, fully accounted for the association signal at this locus. We replicated significant association of rs40401 with GD in an independent sample collection of 839 north Han Chinese subjects. A combined analysis revealed strong validation of this association (odds ratio (OR(common))=1.63, combined P (P(comb))=4 x 10(-6) in the Recessive disease model). This study provides convincing evidence that the IL3 gene is a susceptibility locus for GD in the Chinese population. | Polymorphisms in the /"interleukin 3"/ gene show strong association with susceptibility to /"Graves' disease"/ in Chinese population. | /"Graves' disease"/ (/"GD"/) is a common organ-specific autoimmune disorder, which is multifactorial and develops in genetically susceptible individuals. We had earlier mapped a susceptibility locus for /"GD"/ to chromosome 5q31-33 in a linkage study. Here we used tag single-nucleotide polymorphisms (SNPs) to search for genetic variants associated with /"GD"/, and examined 19 functional candidate genes in this chromosomal region. We identified 192 polymorphisms by re-sequencing the candidate genes, and selected 51 tagSNPs to genotype in a case-control collection of 1118 south Han Chinese subjects (428 cases and 690 controls). Initial analysis suggested that a non-synonymous SNP rs40401 (P27S) of /"interleukin 3"/ (/"IL3"/) was associated with /"GD"/, and further fine-mapping showed that rs40401, or its perfect proxy SNP rs31480 in the 5' flanking region of /"IL3"/, fully accounted for the association signal at this locus. We replicated significant association of rs40401 with /"GD"/ in an independent sample collection of 839 north Han Chinese subjects. A combined analysis revealed strong validation of this association (odds ratio (OR(common))=1.63, combined P (P(comb))=4 x 10(-6) in the Recessive disease model). This study provides convincing evidence that the /"IL3"/ gene is a susceptibility locus for /"GD"/ in the Chinese population. | [
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"text_name": "Graves' disease"
} | Yes |
19262575 | Polymorphisms in the interleukin 3 gene show strong association with susceptibility to Graves' disease in Chinese population. | Graves' disease (GD) is a common organ-specific autoimmune disorder, which is multifactorial and develops in genetically susceptible individuals. We had earlier mapped a susceptibility locus for GD to chromosome 5q31-33 in a linkage study. Here we used tag single-nucleotide polymorphisms (SNPs) to search for genetic variants associated with GD, and examined 19 functional candidate genes in this chromosomal region. We identified 192 polymorphisms by re-sequencing the candidate genes, and selected 51 tagSNPs to genotype in a case-control collection of 1118 south Han Chinese subjects (428 cases and 690 controls). Initial analysis suggested that a non-synonymous SNP rs40401 (P27S) of interleukin 3 (IL3) was associated with GD, and further fine-mapping showed that rs40401, or its perfect proxy SNP rs31480 in the 5' flanking region of IL3, fully accounted for the association signal at this locus. We replicated significant association of rs40401 with GD in an independent sample collection of 839 north Han Chinese subjects. A combined analysis revealed strong validation of this association (odds ratio (OR(common))=1.63, combined P (P(comb))=4 x 10(-6) in the Recessive disease model). This study provides convincing evidence that the IL3 gene is a susceptibility locus for GD in the Chinese population. | Polymorphisms in the /"interleukin 3"/ gene show strong association with susceptibility to Graves' disease in Chinese population. | Graves' disease (GD) is a common organ-specific /"autoimmune disorder"/, which is multifactorial and develops in genetically susceptible individuals. We had earlier mapped a susceptibility locus for GD to chromosome 5q31-33 in a linkage study. Here we used tag single-nucleotide polymorphisms (SNPs) to search for genetic variants associated with GD, and examined 19 functional candidate genes in this chromosomal region. We identified 192 polymorphisms by re-sequencing the candidate genes, and selected 51 tagSNPs to genotype in a case-control collection of 1118 south Han Chinese subjects (428 cases and 690 controls). Initial analysis suggested that a non-synonymous SNP rs40401 (P27S) of /"interleukin 3"/ (/"IL3"/) was associated with GD, and further fine-mapping showed that rs40401, or its perfect proxy SNP rs31480 in the 5' flanking region of /"IL3"/, fully accounted for the association signal at this locus. We replicated significant association of rs40401 with GD in an independent sample collection of 839 north Han Chinese subjects. A combined analysis revealed strong validation of this association (odds ratio (OR(common))=1.63, combined P (P(comb))=4 x 10(-6) in the Recessive disease model). This study provides convincing evidence that the /"IL3"/ gene is a susceptibility locus for GD in the Chinese population. | [
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19264732 | Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype. | BACKGROUND: The 9q subtelomeric deletion syndrome (9qSTDS) is clinically characterised by moderate to severe mental retardation, childhood hypotonia and facial dysmorphisms. In addition, congenital heart defects, urogenital defects, epilepsy and behavioural problems are frequently observed. The syndrome can be either caused by a submicroscopic 9q34.3 deletion or by intragenic EHMT1 mutations leading to haploinsufficiency of the EHMT1 gene. So far it has not been established if and to what extent other genes in the 9q34.3 region contribute to the phenotype observed in deletion cases. This study reports the largest cohort of 9qSTDS cases so far. METHODS AND RESULTS: By a multiplex ligation dependent probe amplification (MLPA) approach, the authors identified and characterised 16 novel submicroscopic 9q deletions. Direct sequence analysis of the EHMT1 gene in 24 patients exhibiting the 9qSTD phenotype without such deletion identified six patients with an intragenic EHMT1 mutation. Five of these mutations predict a premature termination codon whereas one mutation gives rise to an amino acid substitution in a conserved domain of the protein. CONCLUSIONS: The data do not provide any evidence for phenotype-genotype correlations between size of the deletions or type of mutations and severity of clinical features. Therefore, the authors confirm the EHMT1 gene to be the major determinant of the 9qSTDS phenotype. Interestingly, five of six patients who had reached adulthood had developed severe psychiatric pathology, which may indicate that EHMT1 haploinsufficiency is associated with neurodegeneration in addition to neurodevelopmental defect. | Further clinical and molecular delineation of the 9q /"subtelomeric deletion syndrome"/ supports a major contribution of /"EHMT1"/ haploinsufficiency to the core phenotype. | BACKGROUND: The 9q /"subtelomeric deletion syndrome"/ (9qSTDS) is clinically characterised by moderate to severe mental retardation, childhood hypotonia and facial dysmorphisms. In addition, congenital heart defects, urogenital defects, epilepsy and behavioural problems are frequently observed. The syndrome can be either caused by a submicroscopic 9q34.3 deletion or by intragenic /"EHMT1"/ mutations leading to haploinsufficiency of the /"EHMT1"/ gene. So far it has not been established if and to what extent other genes in the 9q34.3 region contribute to the phenotype observed in deletion cases. This study reports the largest cohort of 9qSTDS cases so far. METHODS AND RESULTS: By a multiplex ligation dependent probe amplification (MLPA) approach, the authors identified and characterised 16 novel submicroscopic 9q deletions. Direct sequence analysis of the /"EHMT1"/ gene in 24 patients exhibiting the 9qSTD phenotype without such deletion identified six patients with an intragenic /"EHMT1"/ mutation. Five of these mutations predict a premature termination codon whereas one mutation gives rise to an amino acid substitution in a conserved domain of the protein. CONCLUSIONS: The data do not provide any evidence for phenotype-genotype correlations between size of the deletions or type of mutations and severity of clinical features. Therefore, the authors confirm the /"EHMT1"/ gene to be the major determinant of the 9qSTDS phenotype. Interestingly, five of six patients who had reached adulthood had developed severe psychiatric pathology, which may indicate that /"EHMT1"/ haploinsufficiency is associated with neurodegeneration in addition to neurodevelopmental defect. | [
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} | Yes |
19264732 | Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype. | BACKGROUND: The 9q subtelomeric deletion syndrome (9qSTDS) is clinically characterised by moderate to severe mental retardation, childhood hypotonia and facial dysmorphisms. In addition, congenital heart defects, urogenital defects, epilepsy and behavioural problems are frequently observed. The syndrome can be either caused by a submicroscopic 9q34.3 deletion or by intragenic EHMT1 mutations leading to haploinsufficiency of the EHMT1 gene. So far it has not been established if and to what extent other genes in the 9q34.3 region contribute to the phenotype observed in deletion cases. This study reports the largest cohort of 9qSTDS cases so far. METHODS AND RESULTS: By a multiplex ligation dependent probe amplification (MLPA) approach, the authors identified and characterised 16 novel submicroscopic 9q deletions. Direct sequence analysis of the EHMT1 gene in 24 patients exhibiting the 9qSTD phenotype without such deletion identified six patients with an intragenic EHMT1 mutation. Five of these mutations predict a premature termination codon whereas one mutation gives rise to an amino acid substitution in a conserved domain of the protein. CONCLUSIONS: The data do not provide any evidence for phenotype-genotype correlations between size of the deletions or type of mutations and severity of clinical features. Therefore, the authors confirm the EHMT1 gene to be the major determinant of the 9qSTDS phenotype. Interestingly, five of six patients who had reached adulthood had developed severe psychiatric pathology, which may indicate that EHMT1 haploinsufficiency is associated with neurodegeneration in addition to neurodevelopmental defect. | Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of /"EHMT1"/ haploinsufficiency to the core phenotype. | BACKGROUND: The 9q subtelomeric deletion syndrome (9qSTDS) is clinically characterised by moderate to severe mental retardation, childhood hypotonia and facial dysmorphisms. In addition, congenital heart defects, urogenital defects, epilepsy and behavioural problems are frequently observed. The syndrome can be either caused by a submicroscopic 9q34.3 deletion or by intragenic /"EHMT1"/ mutations leading to haploinsufficiency of the /"EHMT1"/ gene. So far it has not been established if and to what extent other genes in the 9q34.3 region contribute to the phenotype observed in deletion cases. This study reports the largest cohort of 9qSTDS cases so far. METHODS AND RESULTS: By a multiplex ligation dependent probe amplification (MLPA) approach, the authors identified and characterised 16 novel submicroscopic 9q deletions. Direct sequence analysis of the /"EHMT1"/ gene in 24 patients exhibiting the 9qSTD phenotype without such deletion identified six patients with an intragenic /"EHMT1"/ mutation. Five of these mutations predict a premature termination codon whereas one mutation gives rise to an amino acid substitution in a conserved domain of the protein. CONCLUSIONS: The data do not provide any evidence for phenotype-genotype correlations between size of the deletions or type of mutations and severity of clinical features. Therefore, the authors confirm the /"EHMT1"/ gene to be the major determinant of the 9qSTDS phenotype. Interestingly, five of six patients who had reached adulthood had developed severe /"psychiatric"/ pathology, which may indicate that /"EHMT1"/ haploinsufficiency is associated with neurodegeneration in addition to neurodevelopmental defect. | [
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19267885 | One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders. | Autism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), Asperger's syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B(12) and the C677T polymorphism of the MTHFR gene in three groups of children diagnosed with AD (n= 15), AS (n= 5) and PDD-NOS (n= 19) and their age- and sex-matched controls (n= 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD-NOS groups, lower plasma levels of methionine (P= 0.01 and P= 0.03, respectively) and alpha-aminobutyrate were observed (P= 0.01 and P= 0.001, respectively). Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum levels of vitamin B(12) and folate were in the normal range. The results of the MTHFR gene analysis showed a normal distribution of the C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs. | One carbon metabolism disturbances and the C677T /"MTHFR"/ gene polymorphism in children with autism spectrum disorders. | Autism spectrum disorders (ASDs), which include the /"prototypic autistic disorder"/ (/"AD"/), Asperger's syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B(12) and the C677T polymorphism of the /"MTHFR"/ gene in three groups of children diagnosed with /"AD"/ (n= 15), AS (n= 5) and PDD-NOS (n= 19) and their age- and sex-matched controls (n= 25). No metabolic disturbances were seen in the AS patients, while in the /"AD"/ and PDD-NOS groups, lower plasma levels of methionine (P= 0.01 and P= 0.03, respectively) and alpha-aminobutyrate were observed (P= 0.01 and P= 0.001, respectively). Only in the /"AD"/ group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in /"AD"/ patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum levels of vitamin B(12) and folate were in the normal range. The results of the /"MTHFR"/ gene analysis showed a normal distribution of the C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in /"AD"/ patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs. | [
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"text_name": "prototypic autistic disorder"
} | Yes |
19267885 | One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders. | Autism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), Asperger's syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B(12) and the C677T polymorphism of the MTHFR gene in three groups of children diagnosed with AD (n= 15), AS (n= 5) and PDD-NOS (n= 19) and their age- and sex-matched controls (n= 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD-NOS groups, lower plasma levels of methionine (P= 0.01 and P= 0.03, respectively) and alpha-aminobutyrate were observed (P= 0.01 and P= 0.001, respectively). Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum levels of vitamin B(12) and folate were in the normal range. The results of the MTHFR gene analysis showed a normal distribution of the C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs. | One carbon metabolism disturbances and the C677T /"MTHFR"/ gene polymorphism in children with /"autism spectrum disorders"/. | /"Autism spectrum disorders"/ (/"ASDs"/), which include the prototypic autistic disorder (AD), Asperger's syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B(12) and the C677T polymorphism of the /"MTHFR"/ gene in three groups of children diagnosed with AD (n= 15), AS (n= 5) and PDD-NOS (n= 19) and their age- and sex-matched controls (n= 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD-NOS groups, lower plasma levels of methionine (P= 0.01 and P= 0.03, respectively) and alpha-aminobutyrate were observed (P= 0.01 and P= 0.001, respectively). Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the /"ASDs"/ groups. The serum levels of vitamin B(12) and folate were in the normal range. The results of the /"MTHFR"/ gene analysis showed a normal distribution of the C677T polymorphism in children with /"ASDs"/, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of /"ASDs"/ and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of /"ASDs"/. | [
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} | No |
19276544 | Implication of GAB2 gene polymorphism in Italian patients with Alzheimer's disease. | A common polymorphism (rs2373115) in the GRB-associated binding protein 2 (GAB2) gene has been recently associated with the risk of developing Alzheimer's disease (AD) in 644 apolipoprotein E (ApoE) epsilon4 carriers. In order to assess the involvement of the GAB2 polymorphism in the risk of developing AD, we analyzed the genotype and allele distributions of the GAB2 rs2373115 polymorphism in 579 Italian subjects. Our results support a possible implication of GAB2 genetic variant in AD. However, the observed association was confined to ApoE epsilon4 non-carriers, thus suggesting a possible role of GAB2 as an independent risk factor for AD. | Implication of GAB2 gene polymorphism in Italian patients with /"Alzheimer's disease"/. | A common polymorphism (rs2373115) in the GRB-associated binding protein 2 (GAB2) gene has been recently associated with the risk of developing /"Alzheimer's disease"/ (/"AD"/) in 644 /"apolipoprotein E"/ (/"ApoE"/) epsilon4 carriers. In order to assess the involvement of the GAB2 polymorphism in the risk of developing /"AD"/, we analyzed the genotype and allele distributions of the GAB2 rs2373115 polymorphism in 579 Italian subjects. Our results support a possible implication of GAB2 genetic variant in /"AD"/. However, the observed association was confined to /"ApoE"/ epsilon4 non-carriers, thus suggesting a possible role of GAB2 as an independent risk factor for /"AD"/. | [
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"text_name": "Alzheimer's disease"
} | Yes |
19276544 | Implication of GAB2 gene polymorphism in Italian patients with Alzheimer's disease. | A common polymorphism (rs2373115) in the GRB-associated binding protein 2 (GAB2) gene has been recently associated with the risk of developing Alzheimer's disease (AD) in 644 apolipoprotein E (ApoE) epsilon4 carriers. In order to assess the involvement of the GAB2 polymorphism in the risk of developing AD, we analyzed the genotype and allele distributions of the GAB2 rs2373115 polymorphism in 579 Italian subjects. Our results support a possible implication of GAB2 genetic variant in AD. However, the observed association was confined to ApoE epsilon4 non-carriers, thus suggesting a possible role of GAB2 as an independent risk factor for AD. | Implication of /"GAB2"/ gene polymorphism in Italian patients with /"Alzheimer's disease"/. | A common polymorphism (rs2373115) in the /"GRB-associated binding protein 2"/ (/"GAB2"/) gene has been recently associated with the risk of developing /"Alzheimer's disease"/ (/"AD"/) in 644 apolipoprotein E (ApoE) epsilon4 carriers. In order to assess the involvement of the /"GAB2"/ polymorphism in the risk of developing /"AD"/, we analyzed the genotype and allele distributions of the /"GAB2"/ rs2373115 polymorphism in 579 Italian subjects. Our results support a possible implication of /"GAB2"/ genetic variant in /"AD"/. However, the observed association was confined to ApoE epsilon4 non-carriers, thus suggesting a possible role of /"GAB2"/ as an independent risk factor for /"AD"/. | [
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"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "Alzheimer's disease"
} | Yes |
19298594 | Mutation analysis of the HAX1 gene in childhood myelodysplastic syndrome. | Mutation analysis of the /"HAX1"/ gene in /"childhood myelodysplastic syndrome"/. | [
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"text_name": "childhood myelodysplastic syndrome"
} | Yes |
||
19300429 | A rare variant in the visfatin gene (NAMPT/PBEF1) is associated with protection from obesity. | Visfatin was recently reported as a novel adipokine encoded by the NAMPT (PBEF1) gene. This study was aimed at investigation of the possibility that single-nucleotide polymorphisms (SNPs) in the visfatin gene are associated with either obesity or type 2 diabetes (T2D). A set of eight "tag-SNPs" were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of NAMPT was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A,A) vs. (A,T + T,T) genotypes, in children (P = 6 x 10(-9)) and in adults (P = 8 x 10(-5)). No other significant (P < 0.05) association was observed with obesity or T2D for this or any other SNP. No association with BMI or waist-to-hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity. | A rare variant in the /"visfatin"/ gene (/"NAMPT"///"PBEF1"/) is associated with protection from /"obesity"/. | /"Visfatin"/ was recently reported as a novel adipokine encoded by the /"NAMPT"/ (/"PBEF1"/) gene. This study was aimed at investigation of the possibility that single-nucleotide polymorphisms (SNPs) in the /"visfatin"/ gene are associated with either /"obesity"/ or type 2 diabetes (T2D). A set of eight "tag-SNPs" were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely /"obese"/ subjects were typed (896 class III /"obese"/ adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of /"NAMPT"/ was associated with severe /"obesity"/, with a minor allele frequency of 1.6% in controls, 0.4% in the class III /"obese"/ adults and, remarkably, 0% in the severely /"obese"/ children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A,A) vs. (A,T + T,T) genotypes, in children (P = 6 x 10(-9)) and in adults (P = 8 x 10(-5)). No other significant (P < 0.05) association was observed with /"obesity"/ or T2D for this or any other SNP. No association with BMI or waist-to-hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe /"obesity"/. | [
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} | {
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"text_name": "obesity"
} | Yes |
19300429 | A rare variant in the visfatin gene (NAMPT/PBEF1) is associated with protection from obesity. | Visfatin was recently reported as a novel adipokine encoded by the NAMPT (PBEF1) gene. This study was aimed at investigation of the possibility that single-nucleotide polymorphisms (SNPs) in the visfatin gene are associated with either obesity or type 2 diabetes (T2D). A set of eight "tag-SNPs" were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of NAMPT was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A,A) vs. (A,T + T,T) genotypes, in children (P = 6 x 10(-9)) and in adults (P = 8 x 10(-5)). No other significant (P < 0.05) association was observed with obesity or T2D for this or any other SNP. No association with BMI or waist-to-hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity. | A rare variant in the /"visfatin"/ gene (/"NAMPT"///"PBEF1"/) is associated with protection from obesity. | /"Visfatin"/ was recently reported as a novel adipokine encoded by the /"NAMPT"/ (/"PBEF1"/) gene. This study was aimed at investigation of the possibility that single-nucleotide polymorphisms (SNPs) in the /"visfatin"/ gene are associated with either obesity or /"type 2 diabetes"/ (/"T2D"/). A set of eight "tag-SNPs" were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 /"T2D"/ individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of /"NAMPT"/ was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A,A) vs. (A,T + T,T) genotypes, in children (P = 6 x 10(-9)) and in adults (P = 8 x 10(-5)). No other significant (P < 0.05) association was observed with obesity or /"T2D"/ for this or any other SNP. No association with BMI or waist-to-hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity. | [
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1930854 | Elevated levels of parathyroid hormone in essential hypertensive patients with increased erythrocyte potassium efflux. | Previous observations suggest that Ca(2+)-dependent K+ efflux is increased in erythrocytes from spontaneously hypertensive rats. On the other hand, it has been reported that hyperparathyroidism induces an increase in Ca(2+)-dependent K+ efflux of human erythrocytes. To investigate whether Ca(2+)-dependent K+ efflux is altered in essential hypertension quinine-sensitive K+ efflux was measured in erythrocytes from 20 normotensive controls and 30 nontreated essential hypertensives. The quinine-sensitive K+ efflux was similar for hypertensive patients (593 +/- 20 mmol/L cells/h) as compared with normotensive controls (532 +/- 34 mmol/L cells/h). Ten hypertensives exhibited values of quinine-sensitive K+ efflux above an upper normal limit of 650 mmol/L cells/h. As compared with controls those patients presented elevated plasma levels of parathyroid hormone (P less than .05). In addition, a positive correlation was found between parathyroid hormone and quinine-sensitive K+ efflux in the above ten hypertensives (R = 0.85, P less than .001). These results suggest that an excess of parathyroid hormone may be involved in the increase of Ca(2+)-dependent K+ efflux present in some essential hypertensive patients. | Elevated levels of /"parathyroid hormone"/ in essential /"hypertensive"/ patients with increased erythrocyte potassium efflux. | Previous observations suggest that Ca(2+)-dependent K+ efflux is increased in erythrocytes from spontaneously /"hypertensive"/ rats. On the other hand, it has been reported that hyperparathyroidism induces an increase in Ca(2+)-dependent K+ efflux of human erythrocytes. To investigate whether Ca(2+)-dependent K+ efflux is altered in essential /"hypertension"/ quinine-sensitive K+ efflux was measured in erythrocytes from 20 normotensive controls and 30 nontreated essential /"hypertensives"/. The quinine-sensitive K+ efflux was similar for /"hypertensive"/ patients (593 +/- 20 mmol/L cells/h) as compared with normotensive controls (532 +/- 34 mmol/L cells/h). Ten /"hypertensives"/ exhibited values of quinine-sensitive K+ efflux above an upper normal limit of 650 mmol/L cells/h. As compared with controls those patients presented elevated plasma levels of /"parathyroid hormone"/ (P less than .05). In addition, a positive correlation was found between /"parathyroid hormone"/ and quinine-sensitive K+ efflux in the above ten /"hypertensives"/ (R = 0.85, P less than .001). These results suggest that an excess of /"parathyroid hormone"/ may be involved in the increase of Ca(2+)-dependent K+ efflux present in some essential /"hypertensive"/ patients. | [
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1930854 | Elevated levels of parathyroid hormone in essential hypertensive patients with increased erythrocyte potassium efflux. | Previous observations suggest that Ca(2+)-dependent K+ efflux is increased in erythrocytes from spontaneously hypertensive rats. On the other hand, it has been reported that hyperparathyroidism induces an increase in Ca(2+)-dependent K+ efflux of human erythrocytes. To investigate whether Ca(2+)-dependent K+ efflux is altered in essential hypertension quinine-sensitive K+ efflux was measured in erythrocytes from 20 normotensive controls and 30 nontreated essential hypertensives. The quinine-sensitive K+ efflux was similar for hypertensive patients (593 +/- 20 mmol/L cells/h) as compared with normotensive controls (532 +/- 34 mmol/L cells/h). Ten hypertensives exhibited values of quinine-sensitive K+ efflux above an upper normal limit of 650 mmol/L cells/h. As compared with controls those patients presented elevated plasma levels of parathyroid hormone (P less than .05). In addition, a positive correlation was found between parathyroid hormone and quinine-sensitive K+ efflux in the above ten hypertensives (R = 0.85, P less than .001). These results suggest that an excess of parathyroid hormone may be involved in the increase of Ca(2+)-dependent K+ efflux present in some essential hypertensive patients. | Elevated levels of /"parathyroid hormone"/ in essential hypertensive patients with increased erythrocyte potassium efflux. | Previous observations suggest that Ca(2+)-dependent K+ efflux is increased in erythrocytes from spontaneously hypertensive rats. On the other hand, it has been reported that /"hyperparathyroidism"/ induces an increase in Ca(2+)-dependent K+ efflux of human erythrocytes. To investigate whether Ca(2+)-dependent K+ efflux is altered in essential hypertension quinine-sensitive K+ efflux was measured in erythrocytes from 20 normotensive controls and 30 nontreated essential hypertensives. The quinine-sensitive K+ efflux was similar for hypertensive patients (593 +/- 20 mmol/L cells/h) as compared with normotensive controls (532 +/- 34 mmol/L cells/h). Ten hypertensives exhibited values of quinine-sensitive K+ efflux above an upper normal limit of 650 mmol/L cells/h. As compared with controls those patients presented elevated plasma levels of /"parathyroid hormone"/ (P less than .05). In addition, a positive correlation was found between /"parathyroid hormone"/ and quinine-sensitive K+ efflux in the above ten hypertensives (R = 0.85, P less than .001). These results suggest that an excess of /"parathyroid hormone"/ may be involved in the increase of Ca(2+)-dependent K+ efflux present in some essential hypertensive patients. | [
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19350278 | Mutations in the ROBO2 and SLIT2 genes are rare causes of familial vesico-ureteral reflux. | Familial clustering of vesico-ureteral reflux (VUR) suggests that genetic factors play an important role in the pathogenesis of this condition. The SLIT2 protein and its receptor, ROBO2, have key functions in the formation of the ureteric bud. Two recent studies have found that ROBO2 gene missense mutations are associated with VUR. In the study reported here, we investigated the genetic contribution of the SLIT2 and ROBO2 genes in non-syndromic familial VUR by mutation screening of 54 unrelated patients with primary VUR. Direct sequencing of all 26 exons and the exon-intron boundaries revealed six ROBO2 gene variants, two of which were new. Direct sequencing of all 37 exons and the exon-intron boundaries identified 20 SLIT2 gene variants, two of which were new. One variant, c.4253C > T, which was found in two families, leads to an amino acid substitution in a relatively well-conserved amino acid, p.Ala1418Val, which was predicted to cause an altered secondary structure but to have little impact on the three-dimensional structure. This missense variant did not segregate with VUR in these two families and was not found in 96 control subjects. We conclude that gene variants in ROBO2 and SLIT2 are rare causes of VUR in humans. Our results provide further evidence for the genetic heterogeneity of this disorder. | Mutations in the /"ROBO2"/ and SLIT2 genes are rare causes of /"familial vesico-ureteral reflux"/. | Familial clustering of /"vesico-ureteral reflux"/ (/"VUR"/) suggests that genetic factors play an important role in the pathogenesis of this condition. The SLIT2 protein and its receptor, /"ROBO2"/, have key functions in the formation of the ureteric bud. Two recent studies have found that /"ROBO2"/ gene missense mutations are associated with /"VUR"/. In the study reported here, we investigated the genetic contribution of the SLIT2 and /"ROBO2"/ genes in non-syndromic familial /"VUR"/ by mutation screening of 54 unrelated patients with primary /"VUR"/. Direct sequencing of all 26 exons and the exon-intron boundaries revealed six /"ROBO2"/ gene variants, two of which were new. Direct sequencing of all 37 exons and the exon-intron boundaries identified 20 SLIT2 gene variants, two of which were new. One variant, c.4253C > T, which was found in two families, leads to an amino acid substitution in a relatively well-conserved amino acid, p.Ala1418Val, which was predicted to cause an altered secondary structure but to have little impact on the three-dimensional structure. This missense variant did not segregate with /"VUR"/ in these two families and was not found in 96 control subjects. We conclude that gene variants in /"ROBO2"/ and SLIT2 are rare causes of /"VUR"/ in humans. Our results provide further evidence for the genetic heterogeneity of this disorder. | [
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19350278 | Mutations in the ROBO2 and SLIT2 genes are rare causes of familial vesico-ureteral reflux. | Familial clustering of vesico-ureteral reflux (VUR) suggests that genetic factors play an important role in the pathogenesis of this condition. The SLIT2 protein and its receptor, ROBO2, have key functions in the formation of the ureteric bud. Two recent studies have found that ROBO2 gene missense mutations are associated with VUR. In the study reported here, we investigated the genetic contribution of the SLIT2 and ROBO2 genes in non-syndromic familial VUR by mutation screening of 54 unrelated patients with primary VUR. Direct sequencing of all 26 exons and the exon-intron boundaries revealed six ROBO2 gene variants, two of which were new. Direct sequencing of all 37 exons and the exon-intron boundaries identified 20 SLIT2 gene variants, two of which were new. One variant, c.4253C > T, which was found in two families, leads to an amino acid substitution in a relatively well-conserved amino acid, p.Ala1418Val, which was predicted to cause an altered secondary structure but to have little impact on the three-dimensional structure. This missense variant did not segregate with VUR in these two families and was not found in 96 control subjects. We conclude that gene variants in ROBO2 and SLIT2 are rare causes of VUR in humans. Our results provide further evidence for the genetic heterogeneity of this disorder. | Mutations in the ROBO2 and /"SLIT2"/ genes are rare causes of /"familial vesico-ureteral reflux"/. | Familial clustering of /"vesico-ureteral reflux"/ (/"VUR"/) suggests that genetic factors play an important role in the pathogenesis of this condition. The /"SLIT2"/ protein and its receptor, ROBO2, have key functions in the formation of the ureteric bud. Two recent studies have found that ROBO2 gene missense mutations are associated with /"VUR"/. In the study reported here, we investigated the genetic contribution of the /"SLIT2"/ and ROBO2 genes in non-syndromic familial /"VUR"/ by mutation screening of 54 unrelated patients with primary /"VUR"/. Direct sequencing of all 26 exons and the exon-intron boundaries revealed six ROBO2 gene variants, two of which were new. Direct sequencing of all 37 exons and the exon-intron boundaries identified 20 /"SLIT2"/ gene variants, two of which were new. One variant, c.4253C > T, which was found in two families, leads to an amino acid substitution in a relatively well-conserved amino acid, p.Ala1418Val, which was predicted to cause an altered secondary structure but to have little impact on the three-dimensional structure. This missense variant did not segregate with /"VUR"/ in these two families and was not found in 96 control subjects. We conclude that gene variants in ROBO2 and /"SLIT2"/ are rare causes of /"VUR"/ in humans. Our results provide further evidence for the genetic heterogeneity of this disorder. | [
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"text_name": "familial vesico-ureteral reflux"
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19350382 | Investigation of MMAC/PTEN gene mutations and protein expression in low grade gliomas. | The MMAC/PTEN tumor suppressor gene has an essential biological role in the formation of glioblastomas. It is known that there are variations in genetic alterations in tumors that develop in patients with different ethnic backgrounds; thus, we aimed to evaluate the incidence of MMAC/PTEN mutations and protein expression among various low grade gliomas of Turkish patients. We investigated 28 low grade gliomas for mutations of the MMAC/PTEN gene using single strand conformational polymorphism method followed by DNA sequencing. Additionally, the level of MMAC/PTEN protein expression in the tissues of 26 tumors was assessed by immunohistochemistry. In our investigation, MMAC/PTEN mutations were detected in 2 of 28 tumors (7.14%). One novel sequence variant G --> A transition at codon 159 was identified. This missense variation was a result of an alteration from AGG (Arginine) to AAG (Lysine). Moreover, it was observed that MMAC/PTEN protein expression was reduced to 73.08% of tumors. In conclusion, reduced MMAC/PTEN expression by genetic and/or epigenetic mechanisms in low grade gliomas might be associated with glioma tumorigenesis. | Investigation of MMAC//"PTEN"/ gene mutations and protein expression in low grade /"gliomas"/. | The MMAC//"PTEN"/ tumor suppressor gene has an essential biological role in the formation of glioblastomas. It is known that there are variations in genetic alterations in tumors that develop in patients with different ethnic backgrounds; thus, we aimed to evaluate the incidence of MMAC//"PTEN"/ mutations and protein expression among various low grade /"gliomas"/ of Turkish patients. We investigated 28 low grade /"gliomas"/ for mutations of the MMAC//"PTEN"/ gene using single strand conformational polymorphism method followed by DNA sequencing. Additionally, the level of MMAC//"PTEN"/ protein expression in the tissues of 26 tumors was assessed by immunohistochemistry. In our investigation, MMAC//"PTEN"/ mutations were detected in 2 of 28 tumors (7.14%). One novel sequence variant G --> A transition at codon 159 was identified. This missense variation was a result of an alteration from AGG (Arginine) to AAG (Lysine). Moreover, it was observed that MMAC//"PTEN"/ protein expression was reduced to 73.08% of tumors. In conclusion, reduced MMAC//"PTEN"/ expression by genetic and/or epigenetic mechanisms in low grade /"gliomas"/ might be associated with /"glioma tumorigenesis"/. | [
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} | Yes |
19350382 | Investigation of MMAC/PTEN gene mutations and protein expression in low grade gliomas. | The MMAC/PTEN tumor suppressor gene has an essential biological role in the formation of glioblastomas. It is known that there are variations in genetic alterations in tumors that develop in patients with different ethnic backgrounds; thus, we aimed to evaluate the incidence of MMAC/PTEN mutations and protein expression among various low grade gliomas of Turkish patients. We investigated 28 low grade gliomas for mutations of the MMAC/PTEN gene using single strand conformational polymorphism method followed by DNA sequencing. Additionally, the level of MMAC/PTEN protein expression in the tissues of 26 tumors was assessed by immunohistochemistry. In our investigation, MMAC/PTEN mutations were detected in 2 of 28 tumors (7.14%). One novel sequence variant G --> A transition at codon 159 was identified. This missense variation was a result of an alteration from AGG (Arginine) to AAG (Lysine). Moreover, it was observed that MMAC/PTEN protein expression was reduced to 73.08% of tumors. In conclusion, reduced MMAC/PTEN expression by genetic and/or epigenetic mechanisms in low grade gliomas might be associated with glioma tumorigenesis. | Investigation of MMAC//"PTEN"/ gene mutations and protein expression in low grade gliomas. | The MMAC//"PTEN"/ /"tumor"/ suppressor gene has an essential biological role in the formation of glioblastomas. It is known that there are variations in genetic alterations in /"tumors"/ that develop in patients with different ethnic backgrounds; thus, we aimed to evaluate the incidence of MMAC//"PTEN"/ mutations and protein expression among various low grade gliomas of Turkish patients. We investigated 28 low grade gliomas for mutations of the MMAC//"PTEN"/ gene using single strand conformational polymorphism method followed by DNA sequencing. Additionally, the level of MMAC//"PTEN"/ protein expression in the tissues of 26 /"tumors"/ was assessed by immunohistochemistry. In our investigation, MMAC//"PTEN"/ mutations were detected in 2 of 28 /"tumors"/ (7.14%). One novel sequence variant G --> A transition at codon 159 was identified. This missense variation was a result of an alteration from AGG (Arginine) to AAG (Lysine). Moreover, it was observed that MMAC//"PTEN"/ protein expression was reduced to 73.08% of /"tumors"/. In conclusion, reduced MMAC//"PTEN"/ expression by genetic and/or epigenetic mechanisms in low grade gliomas might be associated with glioma tumorigenesis. | [
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19357349 | Association of common genetic variants in SMAD7 and risk of colon cancer. | Two recent genome-wide association studies (GWAS) identified three common variants in SMAD7 (rs4464148, rs4939827 and rs12953717) that confer modest susceptibility to colorectal cancer. Here, we replicated the association of rs4464148 with colon cancer in a population-based case-control study (561 cases and 721 controls). Compared with the TT genotype, those with CT and CC had an adjusted odds ratio (OR) and 95% confidence interval of 1.06 (0.82-1.38) and 1.86 (1.17-2.96), respectively (P(trend) = 0.04). However, stratified analyses revealed that this association was limited to women only [OR = 1.25 (0.88-1.78) for CT and OR = 2.76 (1.53-4.98) for CC, P(trend) = 0.002, P(interaction) = 0.08], which was not noted in any GWAS. Similarly, we found evidence for association with both rs4939827 and rs12953717 in women only (P = 0.007 in dominant rs4939827 model and P = 0.015 in recessive rs12953717 model), but not in men (P > 0.05) and evidence of an interaction with gender (P = 0.015 for rs4939827 and P = 0.061 for rs12953717). Similar effect modification was found in haplotype analyses. Our data add evidence supporting these genetic variants as markers predisposing to colon cancer, specifically in women. | Association of common genetic variants in /"SMAD7"/ and risk of /"colon cancer"/. | Two recent genome-wide association studies (GWAS) identified three common variants in /"SMAD7"/ (rs4464148, rs4939827 and rs12953717) that confer modest susceptibility to colorectal cancer. Here, we replicated the association of rs4464148 with /"colon cancer"/ in a population-based case-control study (561 cases and 721 controls). Compared with the TT genotype, those with CT and CC had an adjusted odds ratio (OR) and 95% confidence interval of 1.06 (0.82-1.38) and 1.86 (1.17-2.96), respectively (P(trend) = 0.04). However, stratified analyses revealed that this association was limited to women only [OR = 1.25 (0.88-1.78) for CT and OR = 2.76 (1.53-4.98) for CC, P(trend) = 0.002, P(interaction) = 0.08], which was not noted in any GWAS. Similarly, we found evidence for association with both rs4939827 and rs12953717 in women only (P = 0.007 in dominant rs4939827 model and P = 0.015 in recessive rs12953717 model), but not in men (P > 0.05) and evidence of an interaction with gender (P = 0.015 for rs4939827 and P = 0.061 for rs12953717). Similar effect modification was found in haplotype analyses. Our data add evidence supporting these genetic variants as markers predisposing to /"colon cancer"/, specifically in women. | [
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"text_name": "colon cancer"
} | Yes |
19357349 | Association of common genetic variants in SMAD7 and risk of colon cancer. | Two recent genome-wide association studies (GWAS) identified three common variants in SMAD7 (rs4464148, rs4939827 and rs12953717) that confer modest susceptibility to colorectal cancer. Here, we replicated the association of rs4464148 with colon cancer in a population-based case-control study (561 cases and 721 controls). Compared with the TT genotype, those with CT and CC had an adjusted odds ratio (OR) and 95% confidence interval of 1.06 (0.82-1.38) and 1.86 (1.17-2.96), respectively (P(trend) = 0.04). However, stratified analyses revealed that this association was limited to women only [OR = 1.25 (0.88-1.78) for CT and OR = 2.76 (1.53-4.98) for CC, P(trend) = 0.002, P(interaction) = 0.08], which was not noted in any GWAS. Similarly, we found evidence for association with both rs4939827 and rs12953717 in women only (P = 0.007 in dominant rs4939827 model and P = 0.015 in recessive rs12953717 model), but not in men (P > 0.05) and evidence of an interaction with gender (P = 0.015 for rs4939827 and P = 0.061 for rs12953717). Similar effect modification was found in haplotype analyses. Our data add evidence supporting these genetic variants as markers predisposing to colon cancer, specifically in women. | Association of common genetic variants in /"SMAD7"/ and risk of colon cancer. | Two recent genome-wide association studies (GWAS) identified three common variants in /"SMAD7"/ (rs4464148, rs4939827 and rs12953717) that confer modest susceptibility to /"colorectal cancer"/. Here, we replicated the association of rs4464148 with colon cancer in a population-based case-control study (561 cases and 721 controls). Compared with the TT genotype, those with CT and CC had an adjusted odds ratio (OR) and 95% confidence interval of 1.06 (0.82-1.38) and 1.86 (1.17-2.96), respectively (P(trend) = 0.04). However, stratified analyses revealed that this association was limited to women only [OR = 1.25 (0.88-1.78) for CT and OR = 2.76 (1.53-4.98) for CC, P(trend) = 0.002, P(interaction) = 0.08], which was not noted in any GWAS. Similarly, we found evidence for association with both rs4939827 and rs12953717 in women only (P = 0.007 in dominant rs4939827 model and P = 0.015 in recessive rs12953717 model), but not in men (P > 0.05) and evidence of an interaction with gender (P = 0.015 for rs4939827 and P = 0.061 for rs12953717). Similar effect modification was found in haplotype analyses. Our data add evidence supporting these genetic variants as markers predisposing to colon cancer, specifically in women. | [
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} | No |
19358091 | Glucokinase gene mutation screening in Argentinean clinically characterized MODY patients. | INTRODUCTION: Mutations in the glucokinase gene (GCK) produce a subtype of Maturity onset diabetes in the young (MODY), named MODY 2. To date over than 190 different mutations have been identified, distributed over the coding regions and the exon-intron boundaries of the gene. The aim of this work was to study the nature and frequency of mutations in the GCK gene, in a MODY clinically characterized Argentinean population. MATERIAL AND METHODS: Seventy unrelated individuals were selected based on MODY clinical features. The study methodology consisted in PCR amplification of the coding regions of the GCK gene, SSCP electrophoresis analysis of the amplified fragments and direct sequencing of the fragments with abnormal electrophoresis pattern. RESULTS: We identified a total of six patients with mutations in the GCK gene. This included two novel mutations: g.1831C>A, g.3792T>A, one already reported by our group, g.168fsdelC (same mutation in two non-related patients) and two already reported: p.Gln138Pro and p.Gly261Glu. With that data, we could establish the prevalence of MODY 2 among the patients in study reaching to 8.6%. DISCUSSION: The main contribution of this study is to inform about two novel mutations not described to date and to make an approach to the establishment of the prevalence of MODY 2 in the population under study. These findings contribute to confirm the allelic heterogeneity of GCK gene mutations and may provide an insight into the structure-function relationship of the GCK. | /"Glucokinase"/ gene mutation screening in Argentinean clinically characterized /"MODY"/ patients. | INTRODUCTION: Mutations in the /"glucokinase"/ gene (/"GCK"/) produce a subtype of /"Maturity onset diabetes in the young"/ (/"MODY"/), named /"MODY 2"/. To date over than 190 different mutations have been identified, distributed over the coding regions and the exon-intron boundaries of the gene. The aim of this work was to study the nature and frequency of mutations in the /"GCK"/ gene, in a /"MODY"/ clinically characterized Argentinean population. MATERIAL AND METHODS: Seventy unrelated individuals were selected based on /"MODY"/ clinical features. The study methodology consisted in PCR amplification of the coding regions of the /"GCK"/ gene, SSCP electrophoresis analysis of the amplified fragments and direct sequencing of the fragments with abnormal electrophoresis pattern. RESULTS: We identified a total of six patients with mutations in the /"GCK"/ gene. This included two novel mutations: g.1831C>A, g.3792T>A, one already reported by our group, g.168fsdelC (same mutation in two non-related patients) and two already reported: p.Gln138Pro and p.Gly261Glu. With that data, we could establish the prevalence of /"MODY 2"/ among the patients in study reaching to 8.6%. DISCUSSION: The main contribution of this study is to inform about two novel mutations not described to date and to make an approach to the establishment of the prevalence of /"MODY 2"/ in the population under study. These findings contribute to confirm the allelic heterogeneity of /"GCK"/ gene mutations and may provide an insight into the structure-function relationship of the /"GCK"/. | [
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19360657 | Family-Based Association Testing of OCD-associated SNPs of SLC1A1 in an autism sample. | Reports identified the neuronal glutamate transporter gene, SLC1A1 (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make SLC1A1 a candidate gene for ASD as well. To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons. | Family-Based Association Testing of OCD-associated SNPs of /"SLC1A1"/ in an /"autism"/ sample. | Reports identified the neuronal glutamate transporter gene, /"SLC1A1"/ (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in /"autism"/, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make /"SLC1A1"/ a candidate gene for /"ASD"/ as well. To test for association between /"SLC1A1"/ and /"autism"/, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with /"autism"/. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between /"autism"/ and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with /"autism"/ (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons. | [
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19360657 | Family-Based Association Testing of OCD-associated SNPs of SLC1A1 in an autism sample. | Reports identified the neuronal glutamate transporter gene, SLC1A1 (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make SLC1A1 a candidate gene for ASD as well. To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons. | Family-Based Association Testing of OCD-associated SNPs of /"SLC1A1"/ in an autism sample. | Reports identified the neuronal glutamate transporter gene, /"SLC1A1"/ (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with /"autism spectrum disorders"/ (/"ASDs"/), and the hypothesized role of glutamate in /"ASDs"/ make /"SLC1A1"/ a candidate gene for ASD as well. To test for association between /"SLC1A1"/ and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons. | [
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19360675 | A large-scale screen for coding variants in SERT/SLC6A4 in autism spectrum disorders. | In the current study we explored the hypothesis that rare variants in SLC6A4 contribute to autism susceptibility and to rigid-compulsive behaviors in autism. We made use of a large number of unrelated cases with autism spectrum disorders (approximately 350) and controls (approximately 420) and screened for rare exonic variants in SLC6A4 by a high-throughput method followed by sequencing. We observed no difference in the frequency of such variants in the two groups, irrespective of how we defined the rare variants. Furthermore, we did not observe an association of rare coding variants in SLC6A4 with rigid-compulsive traits scores in the cases. These results do not support a significant role for rare coding variants in SLC6A4 in autism spectrum disorders, nor do they support a significant role for SLC6A4 in rigid-compulsive traits in these disorders. | A large-scale screen for coding variants in /"SERT"///"SLC6A4"/ in autism spectrum disorders. | In the current study we explored the hypothesis that rare variants in /"SLC6A4"/ contribute to /"autism"/ susceptibility and to rigid-compulsive behaviors in /"autism"/. We made use of a large number of unrelated cases with autism spectrum disorders (approximately 350) and controls (approximately 420) and screened for rare exonic variants in /"SLC6A4"/ by a high-throughput method followed by sequencing. We observed no difference in the frequency of such variants in the two groups, irrespective of how we defined the rare variants. Furthermore, we did not observe an association of rare coding variants in /"SLC6A4"/ with rigid-compulsive traits scores in the cases. These results do not support a significant role for rare coding variants in /"SLC6A4"/ in autism spectrum disorders, nor do they support a significant role for /"SLC6A4"/ in rigid-compulsive traits in these disorders. | [
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19360675 | A large-scale screen for coding variants in SERT/SLC6A4 in autism spectrum disorders. | In the current study we explored the hypothesis that rare variants in SLC6A4 contribute to autism susceptibility and to rigid-compulsive behaviors in autism. We made use of a large number of unrelated cases with autism spectrum disorders (approximately 350) and controls (approximately 420) and screened for rare exonic variants in SLC6A4 by a high-throughput method followed by sequencing. We observed no difference in the frequency of such variants in the two groups, irrespective of how we defined the rare variants. Furthermore, we did not observe an association of rare coding variants in SLC6A4 with rigid-compulsive traits scores in the cases. These results do not support a significant role for rare coding variants in SLC6A4 in autism spectrum disorders, nor do they support a significant role for SLC6A4 in rigid-compulsive traits in these disorders. | A large-scale screen for coding variants in /"SERT"///"SLC6A4"/ in /"autism spectrum disorders"/. | In the current study we explored the hypothesis that rare variants in /"SLC6A4"/ contribute to autism susceptibility and to rigid-compulsive behaviors in autism. We made use of a large number of unrelated cases with /"autism spectrum disorders"/ (approximately 350) and controls (approximately 420) and screened for rare exonic variants in /"SLC6A4"/ by a high-throughput method followed by sequencing. We observed no difference in the frequency of such variants in the two groups, irrespective of how we defined the rare variants. Furthermore, we did not observe an association of rare coding variants in /"SLC6A4"/ with rigid-compulsive traits scores in the cases. These results do not support a significant role for rare coding variants in /"SLC6A4"/ in /"autism spectrum disorders"/, nor do they support a significant role for /"SLC6A4"/ in rigid-compulsive traits in these disorders. | [
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19362357 | TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants. | BACKGROUND: The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and blocks T(H)2 commitment together with the homeobox transcription factor HLX1. OBJECTIVE: The role of genetic variants in TBX21 alone and in combination with HLX1 polymorphisms was investigated in the development of T(H)2-associated atopy and asthma. METHODS: The TBX21 gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested asthma case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on TBX21 gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the TBX21 gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood asthma risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). TBX21 promoter polymorphisms contained in 2 blocks significantly influenced TBX21 promoter activity. In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold. CONCLUSIONS: These data suggest that TBX21 polymorphisms contribute to the development of asthma, potentially by altering TBX21 promoter activity. A risk score model indicates that TBX21 and HLX1 polymorphisms may have synergistic effects on asthma risk. | /"TBX21"/ gene variants increase childhood /"asthma"/ risk in combination with HLX1 variants. | BACKGROUND: The T cell-specific T-box transcription factor (/"TBX21"/) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and blocks T(H)2 commitment together with the homeobox transcription factor HLX1. OBJECTIVE: The role of genetic variants in /"TBX21"/ alone and in combination with HLX1 polymorphisms was investigated in the development of T(H)2-associated atopy and /"asthma"/. METHODS: The /"TBX21"/ gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested /"asthma"/ case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on /"TBX21"/ gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of /"TBX21"/ and HLX1 polymorphisms on the development of /"asthma"/ was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the /"TBX21"/ gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood /"asthma"/ risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). /"TBX21"/ promoter polymorphisms contained in 2 blocks significantly influenced /"TBX21"/ promoter activity. In a risk score model, the combination of /"TBX21"/ and HLX1 polymorphisms increased the /"asthma"/ risk by more than 3-fold. CONCLUSIONS: These data suggest that /"TBX21"/ polymorphisms contribute to the development of /"asthma"/, potentially by altering /"TBX21"/ promoter activity. A risk score model indicates that /"TBX21"/ and HLX1 polymorphisms may have synergistic effects on /"asthma"/ risk. | [
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19362357 | TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants. | BACKGROUND: The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and blocks T(H)2 commitment together with the homeobox transcription factor HLX1. OBJECTIVE: The role of genetic variants in TBX21 alone and in combination with HLX1 polymorphisms was investigated in the development of T(H)2-associated atopy and asthma. METHODS: The TBX21 gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested asthma case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on TBX21 gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the TBX21 gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood asthma risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). TBX21 promoter polymorphisms contained in 2 blocks significantly influenced TBX21 promoter activity. In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold. CONCLUSIONS: These data suggest that TBX21 polymorphisms contribute to the development of asthma, potentially by altering TBX21 promoter activity. A risk score model indicates that TBX21 and HLX1 polymorphisms may have synergistic effects on asthma risk. | TBX21 gene variants increase childhood /"asthma"/ risk in combination with /"HLX1"/ variants. | BACKGROUND: The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and blocks T(H)2 commitment together with the homeobox transcription factor /"HLX1"/. OBJECTIVE: The role of genetic variants in TBX21 alone and in combination with /"HLX1"/ polymorphisms was investigated in the development of T(H)2-associated atopy and /"asthma"/. METHODS: The TBX21 gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested /"asthma"/ case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on TBX21 gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of TBX21 and /"HLX1"/ polymorphisms on the development of /"asthma"/ was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the TBX21 gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood /"asthma"/ risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). TBX21 promoter polymorphisms contained in 2 blocks significantly influenced TBX21 promoter activity. In a risk score model, the combination of TBX21 and /"HLX1"/ polymorphisms increased the /"asthma"/ risk by more than 3-fold. CONCLUSIONS: These data suggest that TBX21 polymorphisms contribute to the development of /"asthma"/, potentially by altering TBX21 promoter activity. A risk score model indicates that TBX21 and /"HLX1"/ polymorphisms may have synergistic effects on /"asthma"/ risk. | [
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19362357 | TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants. | BACKGROUND: The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and blocks T(H)2 commitment together with the homeobox transcription factor HLX1. OBJECTIVE: The role of genetic variants in TBX21 alone and in combination with HLX1 polymorphisms was investigated in the development of T(H)2-associated atopy and asthma. METHODS: The TBX21 gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested asthma case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on TBX21 gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the TBX21 gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood asthma risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). TBX21 promoter polymorphisms contained in 2 blocks significantly influenced TBX21 promoter activity. In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold. CONCLUSIONS: These data suggest that TBX21 polymorphisms contribute to the development of asthma, potentially by altering TBX21 promoter activity. A risk score model indicates that TBX21 and HLX1 polymorphisms may have synergistic effects on asthma risk. | /"TBX21"/ gene variants increase childhood asthma risk in combination with HLX1 variants. | BACKGROUND: The T cell-specific T-box transcription factor (/"TBX21"/) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and /"blocks T"/(H)2 commitment together with the homeobox transcription factor HLX1. OBJECTIVE: The role of genetic variants in /"TBX21"/ alone and in combination with HLX1 polymorphisms was investigated in the development of T(H)2-associated atopy and asthma. METHODS: The /"TBX21"/ gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested asthma case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on /"TBX21"/ gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of /"TBX21"/ and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the /"TBX21"/ gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood asthma risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). /"TBX21"/ promoter polymorphisms contained in 2 blocks significantly influenced /"TBX21"/ promoter activity. In a risk score model, the combination of /"TBX21"/ and HLX1 polymorphisms increased the asthma risk by more than 3-fold. CONCLUSIONS: These data suggest that /"TBX21"/ polymorphisms contribute to the development of asthma, potentially by altering /"TBX21"/ promoter activity. A risk score model indicates that /"TBX21"/ and HLX1 polymorphisms may have synergistic effects on asthma risk. | [
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19362357 | TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants. | BACKGROUND: The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and blocks T(H)2 commitment together with the homeobox transcription factor HLX1. OBJECTIVE: The role of genetic variants in TBX21 alone and in combination with HLX1 polymorphisms was investigated in the development of T(H)2-associated atopy and asthma. METHODS: The TBX21 gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested asthma case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on TBX21 gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the TBX21 gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood asthma risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). TBX21 promoter polymorphisms contained in 2 blocks significantly influenced TBX21 promoter activity. In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold. CONCLUSIONS: These data suggest that TBX21 polymorphisms contribute to the development of asthma, potentially by altering TBX21 promoter activity. A risk score model indicates that TBX21 and HLX1 polymorphisms may have synergistic effects on asthma risk. | TBX21 gene variants increase childhood asthma risk in combination with /"HLX1"/ variants. | BACKGROUND: The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and /"blocks T"/(H)2 commitment together with the homeobox transcription factor /"HLX1"/. OBJECTIVE: The role of genetic variants in TBX21 alone and in combination with /"HLX1"/ polymorphisms was investigated in the development of T(H)2-associated atopy and asthma. METHODS: The TBX21 gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested asthma case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on TBX21 gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of TBX21 and /"HLX1"/ polymorphisms on the development of asthma was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the TBX21 gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood asthma risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). TBX21 promoter polymorphisms contained in 2 blocks significantly influenced TBX21 promoter activity. In a risk score model, the combination of TBX21 and /"HLX1"/ polymorphisms increased the asthma risk by more than 3-fold. CONCLUSIONS: These data suggest that TBX21 polymorphisms contribute to the development of asthma, potentially by altering TBX21 promoter activity. A risk score model indicates that TBX21 and /"HLX1"/ polymorphisms may have synergistic effects on asthma risk. | [
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19363267 | Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes. | We studied eight polymorphisms within APOE, PRNP, PRND, and CYP46 genes in 213 Polish late-onset patients with Alzheimer's disease (AD) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with AD and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for AD was found for individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. AD can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for AD. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles. | Earlier onset of /"Alzheimer's disease"/: risk polymorphisms within PRNP, /"PRND"/, CYP46, and APOE genes. | We studied eight polymorphisms within APOE, PRNP, /"PRND"/, and CYP46 genes in 213 Polish late-onset patients with /"Alzheimer's disease"/ (/"AD"/) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with /"AD"/ and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for /"AD"/ was found for individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, /"PRND"/ codon 174 Thr allele, and CYP46 rs754203 g allele. /"AD"/ can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for /"AD"/. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles. | [
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19363267 | Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes. | We studied eight polymorphisms within APOE, PRNP, PRND, and CYP46 genes in 213 Polish late-onset patients with Alzheimer's disease (AD) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with AD and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for AD was found for individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. AD can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for AD. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles. | Earlier onset of /"Alzheimer's disease"/: risk polymorphisms within PRNP, PRND, CYP46, and /"APOE"/ genes. | We studied eight polymorphisms within /"APOE"/, PRNP, PRND, and CYP46 genes in 213 Polish late-onset patients with /"Alzheimer's disease"/ (/"AD"/) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with /"AD"/ and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for /"AD"/ was found for individuals who co-inherited /"APOE"/ epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. /"AD"/ can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for /"AD"/. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles. | [
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19363267 | Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes. | We studied eight polymorphisms within APOE, PRNP, PRND, and CYP46 genes in 213 Polish late-onset patients with Alzheimer's disease (AD) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with AD and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for AD was found for individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. AD can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for AD. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles. | Earlier onset of /"Alzheimer's disease"/: risk polymorphisms within PRNP, PRND, /"CYP46"/, and APOE genes. | We studied eight polymorphisms within APOE, PRNP, PRND, and /"CYP46"/ genes in 213 Polish late-onset patients with /"Alzheimer's disease"/ (/"AD"/) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with /"AD"/ and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for /"AD"/ was found for individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and /"CYP46"/ rs754203 g allele. /"AD"/ can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for /"AD"/. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles. | [
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19363267 | Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes. | We studied eight polymorphisms within APOE, PRNP, PRND, and CYP46 genes in 213 Polish late-onset patients with Alzheimer's disease (AD) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with AD and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for AD was found for individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. AD can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for AD. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles. | Earlier onset of /"Alzheimer's disease"/: risk polymorphisms within /"PRNP"/, PRND, CYP46, and APOE genes. | We studied eight polymorphisms within APOE, /"PRNP"/, PRND, and CYP46 genes in 213 Polish late-onset patients with /"Alzheimer's disease"/ (/"AD"/) and 171 non-demented elderly controls. A latent classification approach, grade-of-membership analysis, was taken to identify three extreme pure type risk sets defined by the probabilities of being affected with /"AD"/ and for genotypes found at the examined genes. Sets I and II represented high intrinsic risk, having a higher density of various genotypes compared to set III, at low intrinsic risk. A gradient of onset age depending on membership in the risk sets was also observed. Logistic regression analysis showed that the highest risk for /"AD"/ was found for individuals who co-inherited APOE epsilon4 allele, /"PRNP"/ codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. /"AD"/ can be influenced by genetic profiles leading to appearance of the disease, composed of genes which separately evoke a little or unnoticeable effect. Moreover, there may be multiple sufficient risk sets for /"AD"/. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles. | [
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} | Yes |
19364291 | Dopamine-related genotypes and the dose-response effect of methylphenidate on eating in attention-deficit/hyperactivity disorder youths. | OBJECTIVE: There are individual differences in the effects of methylphenidate (MPH), a dopamine (DA) transport inhibitor, on appetite in children with attention-deficit/hyperactivity disorder (ADHD). One potential moderating factor is variation in brain DA activity, which is influenced by dopamine-related genes: the DA transporter (DAT) (SLC6A3), the DA D2 receptor (DRD2), and the DA D4 receptor (DRD4) genes. The purpose of this study was to explore the relationship between dopamine-related gene polymorphisms and food consumption in ADHD children receiving varying doses of MPH. METHODS: In a randomized, within-subject, double-blind design, 58 ADHD children (ages 6-12 years) received placebo, 0.15, 0.3, or 0.6 mg/kg of MPH three times daily over 9 weeks. Observations of percent lunch consumed as a function of dopamine-related genotypes and MPH dose were analyzed using mixed effects regression models. RESULTS: A significant dose-response reduction in eating was observed across all genotypes (p < 0.001). There was an interaction of DAT SLC6A3 and DRD2 genotypes and dose, because 9/9 DAT children showed a stronger effect of dose when compared with the 9/10 and 10/10 children (p < 0.001) and DRD2 A2/A2 children showed a stronger effect of dose when compared with A1/A1 and A1/A2 children combined (p = 0.007). There was no significant interaction of dose by DRD4 genotype. CONCLUSIONS: Lunch consumption decreased as a function of MPH dose. DA-related genotypes associated with greater brain DA signaling moderated the influence of drug on consumption. These results provide information relevant to predicting which children are likely to experience the greatest appetite suppression when taking MPH. | Dopamine-related genotypes and the dose-response effect of methylphenidate on eating in /"attention-deficit/hyperactivity disorder"/ youths. | OBJECTIVE: There are individual differences in the effects of methylphenidate (MPH), a dopamine (DA) transport inhibitor, on appetite in children with /"attention-deficit/hyperactivity disorder"/ (/"ADHD"/). One potential moderating factor is variation in brain DA activity, which is influenced by dopamine-related genes: the DA transporter (DAT) (SLC6A3), the DA D2 receptor (/"DRD2"/), and the DA D4 receptor (DRD4) genes. The purpose of this study was to explore the relationship between dopamine-related gene polymorphisms and food consumption in /"ADHD"/ children receiving varying doses of MPH. METHODS: In a randomized, within-subject, double-blind design, 58 /"ADHD"/ children (ages 6-12 years) received placebo, 0.15, 0.3, or 0.6 mg/kg of MPH three times daily over 9 weeks. Observations of percent lunch consumed as a function of dopamine-related genotypes and MPH dose were analyzed using mixed effects regression models. RESULTS: A significant dose-response reduction in eating was observed across all genotypes (p < 0.001). There was an interaction of DAT SLC6A3 and /"DRD2"/ genotypes and dose, because 9/9 DAT children showed a stronger effect of dose when compared with the 9/10 and 10/10 children (p < 0.001) and /"DRD2"/ A2/A2 children showed a stronger effect of dose when compared with A1/A1 and A1/A2 children combined (p = 0.007). There was no significant interaction of dose by DRD4 genotype. CONCLUSIONS: Lunch consumption decreased as a function of MPH dose. DA-related genotypes associated with greater brain DA signaling moderated the influence of drug on consumption. These results provide information relevant to predicting which children are likely to experience the greatest appetite suppression when taking MPH. | [
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"begin_idx": "88",
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"entity_id": "D001289",
"entity_type": "Disease",
"text_name": "attention-deficit/hyperactivity disorder"
} | Yes |
19364291 | Dopamine-related genotypes and the dose-response effect of methylphenidate on eating in attention-deficit/hyperactivity disorder youths. | OBJECTIVE: There are individual differences in the effects of methylphenidate (MPH), a dopamine (DA) transport inhibitor, on appetite in children with attention-deficit/hyperactivity disorder (ADHD). One potential moderating factor is variation in brain DA activity, which is influenced by dopamine-related genes: the DA transporter (DAT) (SLC6A3), the DA D2 receptor (DRD2), and the DA D4 receptor (DRD4) genes. The purpose of this study was to explore the relationship between dopamine-related gene polymorphisms and food consumption in ADHD children receiving varying doses of MPH. METHODS: In a randomized, within-subject, double-blind design, 58 ADHD children (ages 6-12 years) received placebo, 0.15, 0.3, or 0.6 mg/kg of MPH three times daily over 9 weeks. Observations of percent lunch consumed as a function of dopamine-related genotypes and MPH dose were analyzed using mixed effects regression models. RESULTS: A significant dose-response reduction in eating was observed across all genotypes (p < 0.001). There was an interaction of DAT SLC6A3 and DRD2 genotypes and dose, because 9/9 DAT children showed a stronger effect of dose when compared with the 9/10 and 10/10 children (p < 0.001) and DRD2 A2/A2 children showed a stronger effect of dose when compared with A1/A1 and A1/A2 children combined (p = 0.007). There was no significant interaction of dose by DRD4 genotype. CONCLUSIONS: Lunch consumption decreased as a function of MPH dose. DA-related genotypes associated with greater brain DA signaling moderated the influence of drug on consumption. These results provide information relevant to predicting which children are likely to experience the greatest appetite suppression when taking MPH. | Dopamine-related genotypes and the dose-response effect of methylphenidate on eating in /"attention-deficit/hyperactivity disorder"/ youths. | OBJECTIVE: There are individual differences in the effects of methylphenidate (MPH), a dopamine (DA) transport inhibitor, on appetite in children with /"attention-deficit/hyperactivity disorder"/ (/"ADHD"/). One potential moderating factor is variation in brain DA activity, which is influenced by dopamine-related genes: the /"DA transporter"/ (/"DAT"/) (/"SLC6A3"/), the DA D2 receptor (DRD2), and the DA D4 receptor (DRD4) genes. The purpose of this study was to explore the relationship between dopamine-related gene polymorphisms and food consumption in /"ADHD"/ children receiving varying doses of MPH. METHODS: In a randomized, within-subject, double-blind design, 58 /"ADHD"/ children (ages 6-12 years) received placebo, 0.15, 0.3, or 0.6 mg/kg of MPH three times daily over 9 weeks. Observations of percent lunch consumed as a function of dopamine-related genotypes and MPH dose were analyzed using mixed effects regression models. RESULTS: A significant dose-response reduction in eating was observed across all genotypes (p < 0.001). There was an interaction of /"DAT"/ /"SLC6A3"/ and DRD2 genotypes and dose, because 9/9 /"DAT"/ children showed a stronger effect of dose when compared with the 9/10 and 10/10 children (p < 0.001) and DRD2 A2/A2 children showed a stronger effect of dose when compared with A1/A1 and A1/A2 children combined (p = 0.007). There was no significant interaction of dose by DRD4 genotype. CONCLUSIONS: Lunch consumption decreased as a function of MPH dose. DA-related genotypes associated with greater brain DA signaling moderated the influence of drug on consumption. These results provide information relevant to predicting which children are likely to experience the greatest appetite suppression when taking MPH. | [
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"text_name": "attention-deficit/hyperactivity disorder"
} | Yes |
19364291 | Dopamine-related genotypes and the dose-response effect of methylphenidate on eating in attention-deficit/hyperactivity disorder youths. | OBJECTIVE: There are individual differences in the effects of methylphenidate (MPH), a dopamine (DA) transport inhibitor, on appetite in children with attention-deficit/hyperactivity disorder (ADHD). One potential moderating factor is variation in brain DA activity, which is influenced by dopamine-related genes: the DA transporter (DAT) (SLC6A3), the DA D2 receptor (DRD2), and the DA D4 receptor (DRD4) genes. The purpose of this study was to explore the relationship between dopamine-related gene polymorphisms and food consumption in ADHD children receiving varying doses of MPH. METHODS: In a randomized, within-subject, double-blind design, 58 ADHD children (ages 6-12 years) received placebo, 0.15, 0.3, or 0.6 mg/kg of MPH three times daily over 9 weeks. Observations of percent lunch consumed as a function of dopamine-related genotypes and MPH dose were analyzed using mixed effects regression models. RESULTS: A significant dose-response reduction in eating was observed across all genotypes (p < 0.001). There was an interaction of DAT SLC6A3 and DRD2 genotypes and dose, because 9/9 DAT children showed a stronger effect of dose when compared with the 9/10 and 10/10 children (p < 0.001) and DRD2 A2/A2 children showed a stronger effect of dose when compared with A1/A1 and A1/A2 children combined (p = 0.007). There was no significant interaction of dose by DRD4 genotype. CONCLUSIONS: Lunch consumption decreased as a function of MPH dose. DA-related genotypes associated with greater brain DA signaling moderated the influence of drug on consumption. These results provide information relevant to predicting which children are likely to experience the greatest appetite suppression when taking MPH. | Dopamine-related genotypes and the dose-response effect of methylphenidate on eating in /"attention-deficit/hyperactivity disorder"/ youths. | OBJECTIVE: There are individual differences in the effects of methylphenidate (MPH), a dopamine (DA) transport inhibitor, on appetite in children with /"attention-deficit/hyperactivity disorder"/ (/"ADHD"/). One potential moderating factor is variation in brain DA activity, which is influenced by dopamine-related genes: the DA transporter (DAT) (SLC6A3), the DA D2 receptor (DRD2), and the /"DA D4 receptor"/ (/"DRD4"/) genes. The purpose of this study was to explore the relationship between dopamine-related gene polymorphisms and food consumption in /"ADHD"/ children receiving varying doses of MPH. METHODS: In a randomized, within-subject, double-blind design, 58 /"ADHD"/ children (ages 6-12 years) received placebo, 0.15, 0.3, or 0.6 mg/kg of MPH three times daily over 9 weeks. Observations of percent lunch consumed as a function of dopamine-related genotypes and MPH dose were analyzed using mixed effects regression models. RESULTS: A significant dose-response reduction in eating was observed across all genotypes (p < 0.001). There was an interaction of DAT SLC6A3 and DRD2 genotypes and dose, because 9/9 DAT children showed a stronger effect of dose when compared with the 9/10 and 10/10 children (p < 0.001) and DRD2 A2/A2 children showed a stronger effect of dose when compared with A1/A1 and A1/A2 children combined (p = 0.007). There was no significant interaction of dose by /"DRD4"/ genotype. CONCLUSIONS: Lunch consumption decreased as a function of MPH dose. DA-related genotypes associated with greater brain DA signaling moderated the influence of drug on consumption. These results provide information relevant to predicting which children are likely to experience the greatest appetite suppression when taking MPH. | [
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19369177 | Association of the 3' region of COMT with schizophrenia in Taiwan. | BACKGROUND/PURPOSE: The Val108/158Met (rs4680) single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene contributes to genetic susceptibility to schizophrenia, which is specifically related to impairments in executive functioning. A different genomic region composed of three SNPs (rs737865, rs4680, rs165599) within the COMT gene has been reported to be significantly associated with schizophrenia in Ashkenazi Jews. This study aims to clarify the association between these three SNPs and their haplotypes with schizophrenia and neurocognitive functioning, using both case-control and family-based designs. METHODS: The case-control study included 124 schizophrenia patients and 112 healthy controls, while the family samples included 83 families with at least two affected siblings. The neurocognitive functioning was assessed by the Continuous Performance Test (CPT) and Wisconsin Card Sorting Test. The association analysis was performed using TRANSMIT and FBAT. RESULTS: There was no significant association between the three SNPs and schizophrenia in the case-control study. In the family study, the A allele of rs165599 was transmitted preferentially to the affected individuals (p = 0.023), and significantly associated with a later age of onset (p = 0.018), more severe delusion/hallucination symptom dimension (p = 0.027), and poorer performance in the CPT (p = 0.04). The triple SNP haplotypes did not reveal any significant association with schizophrenia or neurocognitive function. CONCLUSION: The SNP rs165599, which has been mapped to the 3'-UTR region of the COMT gene, was significantly associated with schizophrenia in our family study, and possibly associated with the age of onset, delusion/hallucination symptom dimension, and CPT performance. Therefore, COMT may contribute to the genetic risk for schizophrenia not through the Val108/158Met polymorphism, but through other variants that are situated 3' to this region, in the Taiwanese population. Nevertheless, the true associated functional variants in our subjects remain to be elucidated. | Association of the 3' region of /"COMT"/ with /"schizophrenia"/ in Taiwan. | BACKGROUND/PURPOSE: The Val108/158Met (rs4680) single nucleotide polymorphism (SNP) in the /"catechol-O-methyltransferase"/ (/"COMT"/) gene contributes to genetic susceptibility to /"schizophrenia"/, which is specifically related to impairments in executive functioning. A different genomic region composed of three SNPs (rs737865, rs4680, rs165599) within the /"COMT"/ gene has been reported to be significantly associated with /"schizophrenia"/ in Ashkenazi Jews. This study aims to clarify the association between these three SNPs and their haplotypes with /"schizophrenia"/ and neurocognitive functioning, using both case-control and family-based designs. METHODS: The case-control study included 124 /"schizophrenia"/ patients and 112 healthy controls, while the family samples included 83 families with at least two affected siblings. The neurocognitive functioning was assessed by the Continuous Performance Test (CPT) and Wisconsin Card Sorting Test. The association analysis was performed using TRANSMIT and FBAT. RESULTS: There was no significant association between the three SNPs and /"schizophrenia"/ in the case-control study. In the family study, the A allele of rs165599 was transmitted preferentially to the affected individuals (p = 0.023), and significantly associated with a later age of onset (p = 0.018), more severe delusion/hallucination symptom dimension (p = 0.027), and poorer performance in the CPT (p = 0.04). The triple SNP haplotypes did not reveal any significant association with /"schizophrenia"/ or neurocognitive function. CONCLUSION: The SNP rs165599, which has been mapped to the 3'-UTR region of the /"COMT"/ gene, was significantly associated with /"schizophrenia"/ in our family study, and possibly associated with the age of onset, delusion/hallucination symptom dimension, and CPT performance. Therefore, /"COMT"/ may contribute to the genetic risk for /"schizophrenia"/ not through the Val108/158Met polymorphism, but through other variants that are situated 3' to this region, in the Taiwanese population. Nevertheless, the true associated functional variants in our subjects remain to be elucidated. | [
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19369177 | Association of the 3' region of COMT with schizophrenia in Taiwan. | BACKGROUND/PURPOSE: The Val108/158Met (rs4680) single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene contributes to genetic susceptibility to schizophrenia, which is specifically related to impairments in executive functioning. A different genomic region composed of three SNPs (rs737865, rs4680, rs165599) within the COMT gene has been reported to be significantly associated with schizophrenia in Ashkenazi Jews. This study aims to clarify the association between these three SNPs and their haplotypes with schizophrenia and neurocognitive functioning, using both case-control and family-based designs. METHODS: The case-control study included 124 schizophrenia patients and 112 healthy controls, while the family samples included 83 families with at least two affected siblings. The neurocognitive functioning was assessed by the Continuous Performance Test (CPT) and Wisconsin Card Sorting Test. The association analysis was performed using TRANSMIT and FBAT. RESULTS: There was no significant association between the three SNPs and schizophrenia in the case-control study. In the family study, the A allele of rs165599 was transmitted preferentially to the affected individuals (p = 0.023), and significantly associated with a later age of onset (p = 0.018), more severe delusion/hallucination symptom dimension (p = 0.027), and poorer performance in the CPT (p = 0.04). The triple SNP haplotypes did not reveal any significant association with schizophrenia or neurocognitive function. CONCLUSION: The SNP rs165599, which has been mapped to the 3'-UTR region of the COMT gene, was significantly associated with schizophrenia in our family study, and possibly associated with the age of onset, delusion/hallucination symptom dimension, and CPT performance. Therefore, COMT may contribute to the genetic risk for schizophrenia not through the Val108/158Met polymorphism, but through other variants that are situated 3' to this region, in the Taiwanese population. Nevertheless, the true associated functional variants in our subjects remain to be elucidated. | Association of the 3' region of /"COMT"/ with schizophrenia in Taiwan. | BACKGROUND/PURPOSE: The Val108/158Met (rs4680) single nucleotide polymorphism (SNP) in the /"catechol-O-methyltransferase"/ (/"COMT"/) gene contributes to genetic susceptibility to schizophrenia, which is specifically related to impairments in executive functioning. A different genomic region composed of three SNPs (rs737865, rs4680, rs165599) within the /"COMT"/ gene has been reported to be significantly associated with schizophrenia in Ashkenazi Jews. This study aims to clarify the association between these three SNPs and their haplotypes with schizophrenia and /"neurocognitive functioning"/, using both case-control and family-based designs. METHODS: The case-control study included 124 schizophrenia patients and 112 healthy controls, while the family samples included 83 families with at least two affected siblings. The /"neurocognitive functioning"/ was assessed by the Continuous Performance Test (CPT) and Wisconsin Card Sorting Test. The association analysis was performed using TRANSMIT and FBAT. RESULTS: There was no significant association between the three SNPs and schizophrenia in the case-control study. In the family study, the A allele of rs165599 was transmitted preferentially to the affected individuals (p = 0.023), and significantly associated with a later age of onset (p = 0.018), more severe delusion/hallucination symptom dimension (p = 0.027), and poorer performance in the CPT (p = 0.04). The triple SNP haplotypes did not reveal any significant association with schizophrenia or /"neurocognitive function"/. CONCLUSION: The SNP rs165599, which has been mapped to the 3'-UTR region of the /"COMT"/ gene, was significantly associated with schizophrenia in our family study, and possibly associated with the age of onset, delusion/hallucination symptom dimension, and CPT performance. Therefore, /"COMT"/ may contribute to the genetic risk for schizophrenia not through the Val108/158Met polymorphism, but through other variants that are situated 3' to this region, in the Taiwanese population. Nevertheless, the true associated functional variants in our subjects remain to be elucidated. | [
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19380028 | Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a Tunisian population. | Cigarette smoking is the predominant risk factor for bladder cancer in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and GSTT1 null genotypes in bladder cancer development in North Tunisia. In all groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1-323.76). | Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on /"bladder cancer"/ in a Tunisian population. | Cigarette smoking is the predominant risk factor for /"bladder cancer"/ in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow /"NAT2"/ variants, and GSTM1 and GSTT1 null genotypes in /"bladder cancer"/ development in North Tunisia. In all groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not appear to be a factor affecting /"bladder cancer"/ susceptibility. For the /"NAT2"/ slow acetylator genotype, the /"NAT2"/*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that /"NAT2"/ slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of /"bladder cancer"/ (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate /"NAT2"/, GSTM1 null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid /"NAT2"/, wild-type GSTM,1 and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1-323.76). | [
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19380028 | Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a Tunisian population. | Cigarette smoking is the predominant risk factor for bladder cancer in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and GSTT1 null genotypes in bladder cancer development in North Tunisia. In all groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1-323.76). | Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on /"bladder cancer"/ in a Tunisian population. | Cigarette smoking is the predominant risk factor for /"bladder cancer"/ in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and /"GSTM1"/ and GSTT1 null genotypes in /"bladder cancer"/ development in North Tunisia. In all groups of patients, we have shown that /"GSTM1"/ and GSTT1 null genotypes did not appear to be a factor affecting /"bladder cancer"/ susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or /"GSTM1"/ null genotypes have a strong increased risk of /"bladder cancer"/ (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, /"GSTM1"/ null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid NAT2, wild-type /"GSTM,1"/ and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1-323.76). | [
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19380028 | Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a Tunisian population. | Cigarette smoking is the predominant risk factor for bladder cancer in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and GSTT1 null genotypes in bladder cancer development in North Tunisia. In all groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1-323.76). | Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on /"bladder cancer"/ in a Tunisian population. | Cigarette smoking is the predominant risk factor for /"bladder cancer"/ in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and /"GSTT1"/ null genotypes in /"bladder cancer"/ development in North Tunisia. In all groups of patients, we have shown that GSTM1 and /"GSTT1"/ null genotypes did not appear to be a factor affecting /"bladder cancer"/ susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type /"GSTT1"/ or GSTM1 null genotypes have a strong increased risk of /"bladder cancer"/ (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type /"GSTT1"/ genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and /"GSTT1"/ null genotypes (p=0.02; OR=12; CI 95% 1-323.76). | [
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19380028 | Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a Tunisian population. | Cigarette smoking is the predominant risk factor for bladder cancer in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and GSTT1 null genotypes in bladder cancer development in North Tunisia. In all groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1-323.76). | Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on /"bladder cancer"/ in a Tunisian population. | Cigarette smoking is the predominant risk factor for /"bladder cancer"/ in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and /"GSTT1"/ null genotypes in /"bladder cancer"/ development in North Tunisia. In all groups of patients, we have shown that GSTM1 and /"GSTT1"/ null genotypes did not appear to be a factor affecting /"bladder cancer"/ susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type /"GSTT1"/ or GSTM1 null genotypes have a strong increased risk of /"bladder cancer"/ (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type /"GSTT1"/ genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and /"GSTT1"/ null genotypes (p=0.02; OR=12; CI 95% 1-323.76). | [
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19383228 | Association between renin-angiotensin system gene polymorphism and recurrent wheezing in Chinese children: a 4-year follow-up study. | This study aimed to clarify the association between angiotensin-converting enzyme (ACE) gene polymorphisms and infant wheezing, and to determine whether an association may contribute to early prediction of persistent wheezing and asthma. The study cohort comprised 149 patients with asthma, 169 patients with wheezing but no clinical diagnosis of asthma and 165 healthy control subjects. The insertion/deletion (I/D) polymorphism of the ACE gene was determined by polymerase chain reaction. Total serum immunoglobulin E was determined for the wheezy group and a 4-year follow-up study was carried out to observe wheezing relapse. Significant differences were found between patients and controls in allele frequency and genotype distribution. The DD genotype was more frequent in patients in the wheezing and asthma groups than in the control subjects. Patients with the DD genotype had a higher frequency of relapse than patients expressing the ID or II genotypes. It is concluded that the DD genotype of ACE is a risk factor for recurrent wheezing in early childhood. | Association between renin-angiotensin system gene polymorphism and recurrent wheezing in Chinese children: a 4-year follow-up study. | This study aimed to clarify the association between /"angiotensin-converting enzyme"/ (/"ACE"/) gene polymorphisms and infant wheezing, and to determine whether an association may contribute to early prediction of persistent wheezing and /"asthma"/. The study cohort comprised 149 patients with /"asthma"/, 169 patients with wheezing but no clinical diagnosis of /"asthma"/ and 165 healthy control subjects. The insertion/deletion (I/D) polymorphism of the /"ACE"/ gene was determined by polymerase chain reaction. Total serum immunoglobulin E was determined for the wheezy group and a 4-year follow-up study was carried out to observe wheezing relapse. Significant differences were found between patients and controls in allele frequency and genotype distribution. The DD genotype was more frequent in patients in the wheezing and /"asthma"/ groups than in the control subjects. Patients with the DD genotype had a higher frequency of relapse than patients expressing the ID or II genotypes. It is concluded that the DD genotype of /"ACE"/ is a risk factor for recurrent wheezing in early childhood. | [
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19383228 | Association between renin-angiotensin system gene polymorphism and recurrent wheezing in Chinese children: a 4-year follow-up study. | This study aimed to clarify the association between angiotensin-converting enzyme (ACE) gene polymorphisms and infant wheezing, and to determine whether an association may contribute to early prediction of persistent wheezing and asthma. The study cohort comprised 149 patients with asthma, 169 patients with wheezing but no clinical diagnosis of asthma and 165 healthy control subjects. The insertion/deletion (I/D) polymorphism of the ACE gene was determined by polymerase chain reaction. Total serum immunoglobulin E was determined for the wheezy group and a 4-year follow-up study was carried out to observe wheezing relapse. Significant differences were found between patients and controls in allele frequency and genotype distribution. The DD genotype was more frequent in patients in the wheezing and asthma groups than in the control subjects. Patients with the DD genotype had a higher frequency of relapse than patients expressing the ID or II genotypes. It is concluded that the DD genotype of ACE is a risk factor for recurrent wheezing in early childhood. | Association between renin-angiotensin system gene polymorphism and recurrent wheezing in Chinese children: a 4-year follow-up study. | This study aimed to clarify the association between /"angiotensin-converting enzyme"/ (/"ACE"/) gene polymorphisms and infant wheezing, and to determine whether an association may contribute to early prediction of persistent wheezing and asthma. The study cohort comprised 149 patients with asthma, 169 patients with wheezing but no clinical diagnosis of asthma and 165 healthy control subjects. The insertion/deletion (I/D) polymorphism of the /"ACE"/ gene was determined by polymerase chain reaction. Total serum immunoglobulin E was determined for the wheezy group and a 4-year follow-up study was carried out to observe wheezing relapse. Significant differences were found between patients and controls in allele frequency and genotype distribution. The /"DD"/ genotype was more frequent in patients in the wheezing and asthma groups than in the control subjects. Patients with the /"DD"/ genotype had a higher frequency of relapse than patients expressing the ID or II genotypes. It is concluded that the /"DD"/ genotype of /"ACE"/ is a risk factor for recurrent wheezing in early childhood. | [
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} | No |
19384265 | The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. | BACKGROUND: Migraine is a prevalent and debilitating disease that may, in part, arise because of disruption in neurovascular endothelia caused by elevated homocysteine. This study examined the homocysteine-lowering effects of vitamin supplementation on migraine disability, frequency and severity and whether MTHFRC677T genotype influenced treatment response. METHODS: This was a randomized, double-blind placebo, controlled trial of 6 months of daily vitamin supplementation (i.e. 2 mg of folic acid, 25 mg vitamin B6, and 400 microg of vitamin B12) in 52 patients diagnosed with migraine with aura. FINDINGS: Vitamin supplementation reduced homocysteine by 39% (approximately 4 mumol/l) compared with baseline, a reduction that was greater then placebo (P=0.001). Vitamin supplementation also reduced the prevalence of migraine disability from 60% at baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for the placebo group (P>0.1). Headache frequency and pain severity were also reduced (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this patient group the treatment effect on both homocysteine levels and migraine disability was associated with MTHFRC677T genotype whereby carriers of the C allele experienced a greater response compared with TT genotypes (P<0.05). INTERPRETATION: This study provides some early evidence that lowering homocysteine through vitamin supplementation reduces migraine disability in a subgroup of patients. Larger trials are now warranted to establish whether vitamin therapy is a safe, inexpensive and effective prophylactic option for treatment of migraine and whether efficacy is dependant on MTHFRC677T genotype. | The effects of vitamin supplementation and /"MTHFR"/ (C677T) genotype on homocysteine-lowering and migraine disability. | BACKGROUND: Migraine is a prevalent and debilitating disease that may, in part, arise because of disruption in neurovascular endothelia caused by elevated homocysteine. This study examined the homocysteine-lowering effects of vitamin supplementation on migraine disability, frequency and severity and whether MTHFRC677T genotype influenced treatment response. METHODS: This was a randomized, double-blind placebo, controlled trial of 6 months of daily vitamin supplementation (i.e. 2 mg of folic acid, 25 mg vitamin B6, and 400 microg of vitamin B12) in 52 patients diagnosed with migraine with aura. FINDINGS: Vitamin supplementation reduced homocysteine by 39% (approximately 4 mumol/l) compared with baseline, a reduction that was greater then placebo (P=0.001). Vitamin supplementation also reduced the prevalence of migraine disability from 60% at baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for the placebo group (P>0.1). Headache frequency and pain severity were also reduced (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this patient group the treatment effect on both homocysteine levels and migraine disability was associated with MTHFRC677T genotype whereby carriers of the C allele experienced a greater response compared with TT genotypes (P<0.05). INTERPRETATION: This study provides some early evidence that lowering homocysteine through vitamin supplementation reduces migraine disability in a subgroup of patients. Larger trials are now warranted to establish whether vitamin therapy is a safe, inexpensive and effective prophylactic option for treatment of /"migraine"/ and whether efficacy is dependant on MTHFRC677T genotype. | [
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19384265 | The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. | BACKGROUND: Migraine is a prevalent and debilitating disease that may, in part, arise because of disruption in neurovascular endothelia caused by elevated homocysteine. This study examined the homocysteine-lowering effects of vitamin supplementation on migraine disability, frequency and severity and whether MTHFRC677T genotype influenced treatment response. METHODS: This was a randomized, double-blind placebo, controlled trial of 6 months of daily vitamin supplementation (i.e. 2 mg of folic acid, 25 mg vitamin B6, and 400 microg of vitamin B12) in 52 patients diagnosed with migraine with aura. FINDINGS: Vitamin supplementation reduced homocysteine by 39% (approximately 4 mumol/l) compared with baseline, a reduction that was greater then placebo (P=0.001). Vitamin supplementation also reduced the prevalence of migraine disability from 60% at baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for the placebo group (P>0.1). Headache frequency and pain severity were also reduced (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this patient group the treatment effect on both homocysteine levels and migraine disability was associated with MTHFRC677T genotype whereby carriers of the C allele experienced a greater response compared with TT genotypes (P<0.05). INTERPRETATION: This study provides some early evidence that lowering homocysteine through vitamin supplementation reduces migraine disability in a subgroup of patients. Larger trials are now warranted to establish whether vitamin therapy is a safe, inexpensive and effective prophylactic option for treatment of migraine and whether efficacy is dependant on MTHFRC677T genotype. | The effects of vitamin supplementation and /"MTHFR"/ (C677T) genotype on homocysteine-lowering and migraine disability. | BACKGROUND: Migraine is a prevalent and debilitating disease that may, in part, arise because of disruption in neurovascular endothelia caused by elevated homocysteine. This study examined the homocysteine-lowering effects of vitamin supplementation on migraine disability, frequency and severity and whether MTHFRC677T genotype influenced treatment response. METHODS: This was a randomized, double-blind placebo, controlled trial of 6 months of daily vitamin supplementation (i.e. 2 mg of folic acid, 25 mg vitamin B6, and 400 microg of vitamin B12) in 52 patients diagnosed with migraine with aura. FINDINGS: Vitamin supplementation reduced homocysteine by 39% (approximately 4 mumol/l) compared with baseline, a reduction that was greater then placebo (P=0.001). Vitamin supplementation also reduced the prevalence of migraine disability from 60% at baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for the placebo group (P>0.1). /"Headache"/ frequency and pain severity were also reduced (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this patient group the treatment effect on both homocysteine levels and migraine disability was associated with MTHFRC677T genotype whereby carriers of the C allele experienced a greater response compared with TT genotypes (P<0.05). INTERPRETATION: This study provides some early evidence that lowering homocysteine through vitamin supplementation reduces migraine disability in a subgroup of patients. Larger trials are now warranted to establish whether vitamin therapy is a safe, inexpensive and effective prophylactic option for treatment of migraine and whether efficacy is dependant on MTHFRC677T genotype. | [
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19388002 | Phenotypic effects of a bipolar liability gene among individuals with major depressive disorder. | Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene. We examined putative phenotypic indicators of bipolarity among patients with major depression and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and depression severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene. | Phenotypic effects of a /"bipolar liability"/ gene among individuals with major depressive disorder. | Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (/"CACNA1C"/) gene have been associated with /"bipolar disorder"/ in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the /"CACNA1C"/ gene. We examined putative phenotypic indicators of /"bipolarity"/ among patients with major depression and elements of longitudinal course suggestive of latent /"bipolarity"/. We also considered remission and depression severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative /"bipolar liability"/ gene. | [
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19388002 | Phenotypic effects of a bipolar liability gene among individuals with major depressive disorder. | Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene. We examined putative phenotypic indicators of bipolarity among patients with major depression and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and depression severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene. | Phenotypic effects of a bipolar liability gene among individuals with major /"depressive disorder"/. | Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (/"CACNA1C"/) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for /"depression"/ for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the /"CACNA1C"/ gene. We examined putative phenotypic indicators of bipolarity among patients with /"major depression"/ and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and /"depression"/ severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline /"depression"/ severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene. | [
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19390641 | Molecular genetic characteristics of X-linked retinoschisis in Koreans. | PURPOSE: X-linked retinoschisis (XLRS) is a recessively inherited disorder that causes macular degeneration and resultant visual defect in young males. Many genetic studies had focused on the patients in Western countries. We characterized the mutational spectrum of the RS1 gene in Korean patients with XLRS, and aimed to provide genetic information of XLRS in an Asian population. METHODS: This study enrolled 17 unrelated probands and their mothers for molecular genetic evaluation. All exons and the flanking intronic regions of RS1 were analyzed by direct sequencing. We performed gene dosage analysis by semiquantitative multiplex PCR to rule out the possibility of duplication in a patient without a sequence variation. We also tried RT-PCR analysis in a case with a putative splicing mutation. RESULTS: Genetic tests revealed 16 Korean patients (94.1%) had RS1 mutations. In one patient, neither sequence variation nor deletion or duplication in RS1 was detected. One case with de novo mutation was confirmed by familial analysis. Identified were 14 causative mutations, three of which were novel: one missense mutation (c.227T>G, p.V76G) and two splice-site mutations (c.78+1G>T and c.78+5G>A). No obvious genotype-phenotype relationship was observed. CONCLUSIONS: A missense mutation was the predominant type, and common or founder mutations were not observed in the Korean patients in this study who had XLRS. This study provides molecular genetic characteristics about an Asian population previously unexplored. The genetic characteristics of Korean XLRS will be helpful for understanding the worldwide spectrum of RS1 mutation. | Molecular genetic characteristics of /"X-linked retinoschisis"/is"/ in Koreans. | PURPOSE: /"X-linked retinoschisis"/is"/ (/"XLRS"/RS"/) is a recessively inherited disorder that causes macular degeneration and resultant visual defect in young males. Many genetic studies had focused on the patients in Western countries. We characterized the mutational spectrum of the /"RS1"/ gene in Korean patients with /"XLRS"/RS"/, and aimed to provide genetic information of /"XLRS"/RS"/ in an Asian population. METHODS: This study enrolled 17 unrelated probands and their mothers for molecular genetic evaluation. All exons and the flanking intronic regions of /"RS1"/ were analyzed by direct sequencing. We performed gene dosage analysis by semiquantitative multiplex PCR to rule out the possibility of duplication in a patient without a sequence variation. We also tried RT-PCR analysis in a case with a putative splicing mutation. RESULTS: Genetic tests revealed 16 Korean patients (94.1%) had /"RS1"/ mutations. In one patient, neither sequence variation nor deletion or duplication in /"RS1"/ was detected. One case with de novo mutation was confirmed by familial analysis. Identified were 14 causative mutations, three of which were novel: one missense mutation (c.227T>G, p.V76G) and two splice-site mutations (c.78+1G>T and c.78+5G>A). No obvious genotype-phenotype relationship was observed. CONCLUSIONS: A missense mutation was the predominant type, and common or founder mutations were not observed in the Korean patients in this study who had /"XLRS"/RS"/. This study provides molecular genetic characteristics about an Asian population previously unexplored. The genetic characteristics of Korean /"XLRS"/RS"/ will be helpful for understanding the worldwide spectrum of /"RS1"/ mutation. | [
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} | {
"begin_idx": "37",
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"entity_type": "Disease",
"text_name": "X-linked retinoschisis"
} | Yes |
19390641 | Molecular genetic characteristics of X-linked retinoschisis in Koreans. | PURPOSE: X-linked retinoschisis (XLRS) is a recessively inherited disorder that causes macular degeneration and resultant visual defect in young males. Many genetic studies had focused on the patients in Western countries. We characterized the mutational spectrum of the RS1 gene in Korean patients with XLRS, and aimed to provide genetic information of XLRS in an Asian population. METHODS: This study enrolled 17 unrelated probands and their mothers for molecular genetic evaluation. All exons and the flanking intronic regions of RS1 were analyzed by direct sequencing. We performed gene dosage analysis by semiquantitative multiplex PCR to rule out the possibility of duplication in a patient without a sequence variation. We also tried RT-PCR analysis in a case with a putative splicing mutation. RESULTS: Genetic tests revealed 16 Korean patients (94.1%) had RS1 mutations. In one patient, neither sequence variation nor deletion or duplication in RS1 was detected. One case with de novo mutation was confirmed by familial analysis. Identified were 14 causative mutations, three of which were novel: one missense mutation (c.227T>G, p.V76G) and two splice-site mutations (c.78+1G>T and c.78+5G>A). No obvious genotype-phenotype relationship was observed. CONCLUSIONS: A missense mutation was the predominant type, and common or founder mutations were not observed in the Korean patients in this study who had XLRS. This study provides molecular genetic characteristics about an Asian population previously unexplored. The genetic characteristics of Korean XLRS will be helpful for understanding the worldwide spectrum of RS1 mutation. | Molecular genetic characteristics of /"X-linked retinoschisis"/ in Koreans. | PURPOSE: /"X-linked retinoschisis"/ (/"XLRS"/) is a recessively inherited disorder that causes /"macular degeneration"/ and resultant visual defect in young males. Many genetic studies had focused on the patients in Western countries. We characterized the mutational spectrum of the /"RS1"/ gene in Korean patients with /"XLRS"/, and aimed to provide genetic information of /"XLRS"/ in an Asian population. METHODS: This study enrolled 17 unrelated probands and their mothers for molecular genetic evaluation. All exons and the flanking intronic regions of /"RS1"/ were analyzed by direct sequencing. We performed gene dosage analysis by semiquantitative multiplex PCR to rule out the possibility of duplication in a patient without a sequence variation. We also tried RT-PCR analysis in a case with a putative splicing mutation. RESULTS: Genetic tests revealed 16 Korean patients (94.1%) had /"RS1"/ mutations. In one patient, neither sequence variation nor deletion or duplication in /"RS1"/ was detected. One case with de novo mutation was confirmed by familial analysis. Identified were 14 causative mutations, three of which were novel: one missense mutation (c.227T>G, p.V76G) and two splice-site mutations (c.78+1G>T and c.78+5G>A). No obvious genotype-phenotype relationship was observed. CONCLUSIONS: A missense mutation was the predominant type, and common or founder mutations were not observed in the Korean patients in this study who had /"XLRS"/. This study provides molecular genetic characteristics about an Asian population previously unexplored. The genetic characteristics of Korean /"XLRS"/ will be helpful for understanding the worldwide spectrum of /"RS1"/ mutation. | [
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} | {
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"entity_id": "D008268",
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"text_name": "macular degeneration"
} | No |
19395426 | Relationship between response to risperidone, plasma concentrations of risperidone and CYP3A4 polymorphisms in schizophrenia patients. | In this study, we examined the relationships between plasma concentrations of risperidone and 9-hydroxyrisperidone and polymorphisms of CYP3A4. All 130 schizophrenia patients (45 men, 85 women, age 15-60 years) who met DSM-IV criteria were given risperidone for 8 weeks. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). CYP3A4*1G was found to be associated with the change in total PANSS scores (Kruskal-Wallis test, P = 0.021), which was not significant on adjusting for multiple testing. Our study has, for the first time, conducted a genetic association study of the CYP3A4 gene with risperidone response. Further studies on larger groups and on the effects of the longer term risperidone treatment are needed to confirm these results. | Relationship between response to risperidone, plasma concentrations of risperidone and /"CYP3A4"/ polymorphisms in /"schizophrenia"/ patients. | In this study, we examined the relationships between plasma concentrations of risperidone and 9-hydroxyrisperidone and polymorphisms of /"CYP3A4"/. All 130 /"schizophrenia"/ patients (45 men, 85 women, age 15-60 years) who met DSM-IV criteria were given risperidone for 8 weeks. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). /"CYP3A4"/*1G was found to be associated with the change in total PANSS scores (Kruskal-Wallis test, P = 0.021), which was not significant on adjusting for multiple testing. Our study has, for the first time, conducted a genetic association study of the /"CYP3A4"/ gene with risperidone response. Further studies on larger groups and on the effects of the longer term risperidone treatment are needed to confirm these results. | [
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"text_name": "schizophrenia"
} | Yes |
19406470 | Comparative analysis of IL6 promoter and receptor polymorphisms in myelodysplasia and multiple myeloma. | The serum levels of interleukin 6 (IL6) are known to be elevated in two diseases of the elderly age, myelodysplastic syndrome (MDS) and multiple myeloma (MM). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating IL6 levels. Scarce and contradictory comparative data are available for MM and to our best knowledge this is the first study on IL6 promoter and IL6 receptor (IL6R) polymorphism in MDS. Therefore we determined the Asp358Ala polymorphism of the IL6 receptor gene and the -174 G>C promoter polymorphism of the IL6 gene in blood samples of 102 MDS and 100 MM patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding IL6 promoter/L-6R. Authors therefore assume other mechanisms causing high IL6 levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of MM and MDS in elderly age. | Comparative analysis of IL6 promoter and receptor polymorphisms in myelodysplasia and /"multiple myeloma"/. | The serum levels of interleukin 6 (IL6) are known to be elevated in two diseases of the elderly age, myelodysplastic syndrome (MDS) and /"multiple myeloma"/ (/"MM"/). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating IL6 levels. Scarce and contradictory comparative data are available for /"MM"/ and to our best knowledge this is the first study on IL6 promoter and /"IL6 receptor"/ (/"IL6R"/) polymorphism in MDS. Therefore we determined the Asp358Ala polymorphism of the /"IL6 receptor"/ gene and the -174 G>C promoter polymorphism of the IL6 gene in blood samples of 102 MDS and 100 /"MM"/ patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding IL6 promoter/L-6R. Authors therefore assume other mechanisms causing high IL6 levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of /"MM"/ and MDS in elderly age. | [
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"text_name": "multiple myeloma"
} | Yes |
19406470 | Comparative analysis of IL6 promoter and receptor polymorphisms in myelodysplasia and multiple myeloma. | The serum levels of interleukin 6 (IL6) are known to be elevated in two diseases of the elderly age, myelodysplastic syndrome (MDS) and multiple myeloma (MM). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating IL6 levels. Scarce and contradictory comparative data are available for MM and to our best knowledge this is the first study on IL6 promoter and IL6 receptor (IL6R) polymorphism in MDS. Therefore we determined the Asp358Ala polymorphism of the IL6 receptor gene and the -174 G>C promoter polymorphism of the IL6 gene in blood samples of 102 MDS and 100 MM patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding IL6 promoter/L-6R. Authors therefore assume other mechanisms causing high IL6 levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of MM and MDS in elderly age. | Comparative analysis of /"IL6"/ promoter and receptor polymorphisms in myelodysplasia and /"multiple myeloma"/. | The serum levels of /"interleukin 6"/ (/"IL6"/) are known to be elevated in two diseases of the elderly age, myelodysplastic syndrome (MDS) and /"multiple myeloma"/ (/"MM"/). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating /"IL6"/ levels. Scarce and contradictory comparative data are available for /"MM"/ and to our best knowledge this is the first study on /"IL6"/ promoter and IL6 receptor (IL6R) polymorphism in MDS. Therefore we determined the Asp358Ala polymorphism of the IL6 receptor gene and the -174 G>C promoter polymorphism of the /"IL6"/ gene in blood samples of 102 MDS and 100 /"MM"/ patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding /"IL6"/ promoter/L-6R. Authors therefore assume other mechanisms causing high /"IL6"/ levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of /"MM"/ and MDS in elderly age. | [
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} | Yes |
19406470 | Comparative analysis of IL6 promoter and receptor polymorphisms in myelodysplasia and multiple myeloma. | The serum levels of interleukin 6 (IL6) are known to be elevated in two diseases of the elderly age, myelodysplastic syndrome (MDS) and multiple myeloma (MM). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating IL6 levels. Scarce and contradictory comparative data are available for MM and to our best knowledge this is the first study on IL6 promoter and IL6 receptor (IL6R) polymorphism in MDS. Therefore we determined the Asp358Ala polymorphism of the IL6 receptor gene and the -174 G>C promoter polymorphism of the IL6 gene in blood samples of 102 MDS and 100 MM patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding IL6 promoter/L-6R. Authors therefore assume other mechanisms causing high IL6 levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of MM and MDS in elderly age. | Comparative analysis of /"IL6"/ promoter and receptor polymorphisms in /"myelodysplasia"/ and multiple myeloma. | The serum levels of /"interleukin 6"/ (/"IL6"/) are known to be elevated in two diseases of the elderly age, /"myelodysplastic syndrome"/ (/"MDS"/) and multiple myeloma (MM). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating /"IL6"/ levels. Scarce and contradictory comparative data are available for MM and to our best knowledge this is the first study on /"IL6"/ promoter and IL6 receptor (IL6R) polymorphism in /"MDS"/. Therefore we determined the Asp358Ala polymorphism of the IL6 receptor gene and the -174 G>C promoter polymorphism of the /"IL6"/ gene in blood samples of 102 /"MDS"/ and 100 MM patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding /"IL6"/ promoter/L-6R. Authors therefore assume other mechanisms causing high /"IL6"/ levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of MM and /"MDS"/ in elderly age. | [
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19406470 | Comparative analysis of IL6 promoter and receptor polymorphisms in myelodysplasia and multiple myeloma. | The serum levels of interleukin 6 (IL6) are known to be elevated in two diseases of the elderly age, myelodysplastic syndrome (MDS) and multiple myeloma (MM). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating IL6 levels. Scarce and contradictory comparative data are available for MM and to our best knowledge this is the first study on IL6 promoter and IL6 receptor (IL6R) polymorphism in MDS. Therefore we determined the Asp358Ala polymorphism of the IL6 receptor gene and the -174 G>C promoter polymorphism of the IL6 gene in blood samples of 102 MDS and 100 MM patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding IL6 promoter/L-6R. Authors therefore assume other mechanisms causing high IL6 levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of MM and MDS in elderly age. | Comparative analysis of IL6 promoter and receptor polymorphisms in /"myelodysplasia"/ and multiple myeloma. | The serum levels of interleukin 6 (IL6) are known to be elevated in two diseases of the elderly age, /"myelodysplastic syndrome"/ (/"MDS"/) and multiple myeloma (MM). Authors suppose that one of the possible causes of this elevation could be a difference between these patients and healthy subjects in the frequency of polymorphic variants of the genes regulating IL6 levels. Scarce and contradictory comparative data are available for MM and to our best knowledge this is the first study on IL6 promoter and /"IL6 receptor"/ (/"IL6R"/) polymorphism in /"MDS"/. Therefore we determined the Asp358Ala polymorphism of the /"IL6 receptor"/ gene and the -174 G>C promoter polymorphism of the IL6 gene in blood samples of 102 /"MDS"/ and 100 MM patients and 99 age- and sex-matched hospitalized controls had been tested for this purpose as well. There was no significant difference between patients with either disease and controls regarding IL6 promoter/L-6R. Authors therefore assume other mechanisms causing high IL6 levels are not related to either of these polymorphisms. Moreover authors consider important to propose a hypothesis how elements of signal transduction in iron metabolism might be involved in the development of MM and /"MDS"/ in elderly age. | [
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19408338 | Filaggrin loss-of-function variants are associated with atopic comorbidity in pediatric inflammatory bowel disease. | BACKGROUND: Pediatric inflammatory bowel disease (IBD) has a high prevalence of coexistent atopy. Filaggrin (FLG) loss-of-function variants (null-alleles) are associated with eczema and asthma in association with eczema. The aim was to assess the contribution of FLG null-alleles to pediatric IBD susceptibility and to coexistent atopy (eczema, asthma, allergic rhinitis, or food allergy). METHODS: FLG variants (R501X and 2282del4) were genotyped in 403 children with IBD, 683 parents, and 996 population controls. RESULTS: In all, 11% of IBD patients carried at least 1 FLG null-allele compared to 11% of population controls (P > 0.4). Carriage of 1 or more null-alleles in patients with atopy (present in 52% of IBD patients) differed from IBD patients without atopy (14% versus 6%, P = 0.01; odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1). The effect of FLG null-alleles was strongest for eczema (19% versus 7%, P = 0.0003; OR 3.3, 95% CI 1.7-6.6) and food allergy (28% versus 8%, P = 0.0001; OR 4.5, 95% CI 2.0-10.0). The presence of more than 1 atopic disease tended to increase the associated OR: eczema + asthma (23% versus 7%, P = 0.001; OR 3.9, 95% CI 1.6-9.1), eczema + asthma + allergic rhinitis (29% versus 7%, P = 0.0006; OR 5.4, 95% CI 1.9-15.4) and eczema + asthma + allergic rhinitis + food allergy (45% versus 6%, P < 10(-4); OR 12.2, 95% CI 3.2-46.3). Logistic regression analysis of IBD cases confirmed the association of carriage of an FLG null-allele with atopy (P = 0.01; OR 2.4, 95% CI 1.2-5.1) and co-occurrence of different forms of atopy (P = 0.003; OR 3.5, 95% CI 1.5-8.1). CONCLUSIONS: Filaggrin null-alleles have no effect on IBD susceptibility but contribute to coexistent eczema and food allergy. | /"Filaggrin"/ loss-of-function variants are associated with atopic comorbidity in pediatric /"inflammatory bowel disease"/. | BACKGROUND: Pediatric /"inflammatory bowel disease"/ (/"IBD"/) has a high prevalence of coexistent atopy. /"Filaggrin"/ (/"FLG"/) loss-of-function variants (null-alleles) are associated with eczema and asthma in association with eczema. The aim was to assess the contribution of /"FLG"/ null-alleles to pediatric /"IBD"/ susceptibility and to coexistent atopy (eczema, asthma, allergic rhinitis, or food allergy). METHODS: /"FLG"/ variants (R501X and 2282del4) were genotyped in 403 children with /"IBD"/, 683 parents, and 996 population controls. RESULTS: In all, 11% of /"IBD"/ patients carried at least 1 /"FLG"/ null-allele compared to 11% of population controls (P > 0.4). Carriage of 1 or more null-alleles in patients with atopy (present in 52% of /"IBD"/ patients) differed from /"IBD"/ patients without atopy (14% versus 6%, P = 0.01; odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1). The effect of /"FLG"/ null-alleles was strongest for eczema (19% versus 7%, P = 0.0003; OR 3.3, 95% CI 1.7-6.6) and food allergy (28% versus 8%, P = 0.0001; OR 4.5, 95% CI 2.0-10.0). The presence of more than 1 atopic disease tended to increase the associated OR: eczema + asthma (23% versus 7%, P = 0.001; OR 3.9, 95% CI 1.6-9.1), eczema + asthma + allergic rhinitis (29% versus 7%, P = 0.0006; OR 5.4, 95% CI 1.9-15.4) and eczema + asthma + allergic rhinitis + food allergy (45% versus 6%, P < 10(-4); OR 12.2, 95% CI 3.2-46.3). Logistic regression analysis of /"IBD"/ cases confirmed the association of carriage of an /"FLG"/ null-allele with atopy (P = 0.01; OR 2.4, 95% CI 1.2-5.1) and co-occurrence of different forms of atopy (P = 0.003; OR 3.5, 95% CI 1.5-8.1). CONCLUSIONS: /"Filaggrin"/ null-alleles have no effect on /"IBD"/ susceptibility but contribute to coexistent eczema and food allergy. | [
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"entity_type": "Gene",
"text_name": "Filaggrin"
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"text_name": "Filaggrin"
} | {
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"entity_type": "Disease",
"text_name": "inflammatory bowel disease"
} | Yes |
19408338 | Filaggrin loss-of-function variants are associated with atopic comorbidity in pediatric inflammatory bowel disease. | BACKGROUND: Pediatric inflammatory bowel disease (IBD) has a high prevalence of coexistent atopy. Filaggrin (FLG) loss-of-function variants (null-alleles) are associated with eczema and asthma in association with eczema. The aim was to assess the contribution of FLG null-alleles to pediatric IBD susceptibility and to coexistent atopy (eczema, asthma, allergic rhinitis, or food allergy). METHODS: FLG variants (R501X and 2282del4) were genotyped in 403 children with IBD, 683 parents, and 996 population controls. RESULTS: In all, 11% of IBD patients carried at least 1 FLG null-allele compared to 11% of population controls (P > 0.4). Carriage of 1 or more null-alleles in patients with atopy (present in 52% of IBD patients) differed from IBD patients without atopy (14% versus 6%, P = 0.01; odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1). The effect of FLG null-alleles was strongest for eczema (19% versus 7%, P = 0.0003; OR 3.3, 95% CI 1.7-6.6) and food allergy (28% versus 8%, P = 0.0001; OR 4.5, 95% CI 2.0-10.0). The presence of more than 1 atopic disease tended to increase the associated OR: eczema + asthma (23% versus 7%, P = 0.001; OR 3.9, 95% CI 1.6-9.1), eczema + asthma + allergic rhinitis (29% versus 7%, P = 0.0006; OR 5.4, 95% CI 1.9-15.4) and eczema + asthma + allergic rhinitis + food allergy (45% versus 6%, P < 10(-4); OR 12.2, 95% CI 3.2-46.3). Logistic regression analysis of IBD cases confirmed the association of carriage of an FLG null-allele with atopy (P = 0.01; OR 2.4, 95% CI 1.2-5.1) and co-occurrence of different forms of atopy (P = 0.003; OR 3.5, 95% CI 1.5-8.1). CONCLUSIONS: Filaggrin null-alleles have no effect on IBD susceptibility but contribute to coexistent eczema and food allergy. | /"Filaggrin"/ loss-of-function variants are associated with atopic comorbidity in pediatric inflammatory bowel disease. | BACKGROUND: Pediatric inflammatory bowel disease (IBD) has a high prevalence of coexistent /"atopy"/. /"Filaggrin"/ (/"FLG"/) loss-of-function variants (null-alleles) are associated with eczema and asthma in association with eczema. The aim was to assess the contribution of /"FLG"/ null-alleles to pediatric IBD susceptibility and to coexistent /"atopy"/ (eczema, asthma, allergic rhinitis, or food allergy). METHODS: /"FLG"/ variants (R501X and 2282del4) were genotyped in 403 children with IBD, 683 parents, and 996 population controls. RESULTS: In all, 11% of IBD patients carried at least 1 /"FLG"/ null-allele compared to 11% of population controls (P > 0.4). Carriage of 1 or more null-alleles in patients with /"atopy"/ (present in 52% of IBD patients) differed from IBD patients without /"atopy"/ (14% versus 6%, P = 0.01; odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1). The effect of /"FLG"/ null-alleles was strongest for eczema (19% versus 7%, P = 0.0003; OR 3.3, 95% CI 1.7-6.6) and food allergy (28% versus 8%, P = 0.0001; OR 4.5, 95% CI 2.0-10.0). The presence of more than 1 atopic disease tended to increase the associated OR: eczema + asthma (23% versus 7%, P = 0.001; OR 3.9, 95% CI 1.6-9.1), eczema + asthma + allergic rhinitis (29% versus 7%, P = 0.0006; OR 5.4, 95% CI 1.9-15.4) and eczema + asthma + allergic rhinitis + food allergy (45% versus 6%, P < 10(-4); OR 12.2, 95% CI 3.2-46.3). Logistic regression analysis of IBD cases confirmed the association of carriage of an /"FLG"/ null-allele with /"atopy"/ (P = 0.01; OR 2.4, 95% CI 1.2-5.1) and co-occurrence of different forms of /"atopy"/ (P = 0.003; OR 3.5, 95% CI 1.5-8.1). CONCLUSIONS: /"Filaggrin"/ null-alleles have no effect on IBD susceptibility but contribute to coexistent eczema and food allergy. | [
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19415413 | CCL8/MCP-2 association analysis in patients with Alzheimer's disease and frontotemporal lobar degeneration. | CCL2/Monocyte Chemoattractant Protein (MCP)-1 and other chemokines sharing a similar sequence, including CCL8/MCP-2, are involved in neurodegeneration. A few Single Nucleotide Polymorphisms (SNPs) have been reported in CCL8/MCP-2, all of which are located in the same linkage block. One of them (rs1163763) leads to an aminoacidic substitution, implying a potential impact on the function of the protein. rs1133763 was tested for association in 219 patients with Alzheimer's disease (AD) and 209 with Frontotemporal Lobar Degeneration (FTLD) as compared with 231 age-matched controls. The distribution of CCL8/MCP-2 rs1133763 was not significantly different among patients with AD or FTLD and controls, even stratifying according to gender. CCL8/MCP rs1133763 SNP, or other variants in linkage disequilibrium with this variant, likely do not influence the susceptibility to AD or FTLD in Caucasians. | /"CCL8"///"MCP-2"/ association analysis in patients with /"Alzheimer's disease"/ and frontotemporal lobar degeneration. | CCL2/Monocyte Chemoattractant Protein (MCP)-1 and other chemokines sharing a similar sequence, including /"CCL8"///"MCP-2"/, are involved in neurodegeneration. A few Single Nucleotide Polymorphisms (SNPs) have been reported in /"CCL8"///"MCP-2"/, all of which are located in the same linkage block. One of them (rs1163763) leads to an aminoacidic substitution, implying a potential impact on the function of the protein. rs1133763 was tested for association in 219 patients with /"Alzheimer's disease"/ (/"AD"/) and 209 with Frontotemporal Lobar Degeneration (FTLD) as compared with 231 age-matched controls. The distribution of /"CCL8"///"MCP-2"/ rs1133763 was not significantly different among patients with /"AD"/ or FTLD and controls, even stratifying according to gender. /"CCL8"//MCP rs1133763 SNP, or other variants in linkage disequilibrium with this variant, likely do not influence the susceptibility to /"AD"/ or FTLD in Caucasians. | [
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} | {
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} | Yes |
19415413 | CCL8/MCP-2 association analysis in patients with Alzheimer's disease and frontotemporal lobar degeneration. | CCL2/Monocyte Chemoattractant Protein (MCP)-1 and other chemokines sharing a similar sequence, including CCL8/MCP-2, are involved in neurodegeneration. A few Single Nucleotide Polymorphisms (SNPs) have been reported in CCL8/MCP-2, all of which are located in the same linkage block. One of them (rs1163763) leads to an aminoacidic substitution, implying a potential impact on the function of the protein. rs1133763 was tested for association in 219 patients with Alzheimer's disease (AD) and 209 with Frontotemporal Lobar Degeneration (FTLD) as compared with 231 age-matched controls. The distribution of CCL8/MCP-2 rs1133763 was not significantly different among patients with AD or FTLD and controls, even stratifying according to gender. CCL8/MCP rs1133763 SNP, or other variants in linkage disequilibrium with this variant, likely do not influence the susceptibility to AD or FTLD in Caucasians. | /"CCL8"///"MCP-2"/ association analysis in patients with Alzheimer's disease and /"frontotemporal lobar degeneration"/. | CCL2/Monocyte Chemoattractant Protein (MCP)-1 and other chemokines sharing a similar sequence, including /"CCL8"///"MCP-2"/, are involved in neurodegeneration. A few Single Nucleotide Polymorphisms (SNPs) have been reported in /"CCL8"///"MCP-2"/, all of which are located in the same linkage block. One of them (rs1163763) leads to an aminoacidic substitution, implying a potential impact on the function of the protein. rs1133763 was tested for association in 219 patients with Alzheimer's disease (AD) and 209 with /"Frontotemporal Lobar Degeneration"/ (/"FTLD"/) as compared with 231 age-matched controls. The distribution of /"CCL8"///"MCP-2"/ rs1133763 was not significantly different among patients with AD or /"FTLD"/ and controls, even stratifying according to gender. /"CCL8"//MCP rs1133763 SNP, or other variants in linkage disequilibrium with this variant, likely do not influence the susceptibility to AD or /"FTLD"/ in Caucasians. | [
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19419979 | Preliminary evidence of a genetic association between tumor necrosis factor alpha and the severity of sleep disturbance and morning fatigue. | Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, tumor necrosis factor-alpha (TNFA-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the TNFA genotype and other covariates on mean sleep disturbance and fatigue scores. Hierarchical linear modeling was used to determine the effect of TNFA genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the TNFA gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers. | Preliminary evidence of a genetic association between /"tumor necrosis factor alpha"/ and the severity of sleep disturbance and morning /"fatigue"/. | Although /"fatigue"/ and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, /"tumor necrosis factor-alpha"/ (/"TNFA"/-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and /"fatigue"/ as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and /"fatigue"/. Multiple linear regression was used to assess the effect of the /"TNFA"/ genotype and other covariates on mean sleep disturbance and /"fatigue"/ scores. Hierarchical linear modeling was used to determine the effect of /"TNFA"/ genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning /"fatigue"/ (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the /"TNFA"/ gene and the severity of sleep disturbance and morning /"fatigue"/ in oncology patients and their family caregivers. | [
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19419979 | Preliminary evidence of a genetic association between tumor necrosis factor alpha and the severity of sleep disturbance and morning fatigue. | Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, tumor necrosis factor-alpha (TNFA-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the TNFA genotype and other covariates on mean sleep disturbance and fatigue scores. Hierarchical linear modeling was used to determine the effect of TNFA genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the TNFA gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers. | Preliminary evidence of a genetic association between /"tumor necrosis factor alpha"/ and the severity of /"sleep disturbance"/ and morning fatigue. | Although fatigue and /"sleep disturbance"/ are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, /"tumor necrosis factor-alpha"/ (/"TNFA"/-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of /"sleep disturbance"/ and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of /"sleep disturbance"/ and fatigue. Multiple linear regression was used to assess the effect of the /"TNFA"/ genotype and other covariates on mean /"sleep disturbance"/ and fatigue scores. Hierarchical linear modeling was used to determine the effect of /"TNFA"/ genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of /"sleep disturbance"/ (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the /"TNFA"/ gene and the severity of /"sleep disturbance"/ and morning fatigue in oncology patients and their family caregivers. | [
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19419979 | Preliminary evidence of a genetic association between tumor necrosis factor alpha and the severity of sleep disturbance and morning fatigue. | Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, tumor necrosis factor-alpha (TNFA-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the TNFA genotype and other covariates on mean sleep disturbance and fatigue scores. Hierarchical linear modeling was used to determine the effect of TNFA genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the TNFA gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers. | Preliminary evidence of a genetic association between /"tumor necrosis factor alpha"/ and the severity of sleep disturbance and morning fatigue. | Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, /"tumor necrosis factor-alpha"/ (/"TNFA"/-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the /"TNFA"/ genotype and other covariates on mean sleep disturbance and fatigue scores. /"Hierarchical linear modeling"/ was used to determine the effect of /"TNFA"/ genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the /"TNFA"/ gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers. | [
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19419979 | Preliminary evidence of a genetic association between tumor necrosis factor alpha and the severity of sleep disturbance and morning fatigue. | Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, tumor necrosis factor-alpha (TNFA-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the TNFA genotype and other covariates on mean sleep disturbance and fatigue scores. Hierarchical linear modeling was used to determine the effect of TNFA genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the TNFA gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers. | Preliminary evidence of a genetic association between /"tumor necrosis factor alpha"/ and the severity of sleep disturbance and morning fatigue. | Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, /"tumor necrosis factor-alpha"/ (/"TNFA"/-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the /"TNFA"/ genotype and other covariates on mean sleep disturbance and fatigue scores. /"Hierarchical linear modeling"/ was used to determine the effect of /"TNFA"/ genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the /"TNFA"/ gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers. | [
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19420919 | E-selectin genetic variation as a susceptibility factor for ischemic stroke. | The polymorphism of the E-selectin gene has been implicated in the pathogenesis of atherosclerosis. We sought to explore whether the allelic variants relate to ischemic stroke. We conducted a case-control study of 359 cases of ischemic stroke and 353 community controls. Participants were evaluated for known cerebrovascular risk factors, and the E-selectin S128R and L554F genotypes were established using the polymerase chain reaction (PCR) method. The frequency of minor allele (R) and heterozygous (RS) genotype of E-selectin S128R polymorphism was significantly higher in the stroke patients than in the controls. Evaluation of genetic variation for E-selectin L554F polymorphisms revealed that the frequency of minor allele (F) and its heterozygous genotype (LF) is almost 4 times higher in the stroke patients than the controls (16.7 vs. 4.3 and 33.4 vs. 8.5, respectively). Multivariable logistic regression analysis after adjustment for age, sex and conventional vascular risk factors demonstrated that alleles R of S128R and F of L554F polymorphisms are independent risk factors for ischemic stroke. The combination of 2 minor alleles of E-selectin genes appeared to be the strongest susceptibility factor for ischemic stroke (adjusted OR: 5.89, 95% CI: 2.84-12.21, p = 0.0001). Our study demonstrates that the E-selectin S128R and L554F polymorphisms are associated with susceptibility to ischemic stroke. | /"E-selectin"/ genetic variation as a susceptibility factor for ischemic stroke. | The polymorphism of the /"E-selectin"/ gene has been implicated in the pathogenesis of atherosclerosis. We sought to explore whether the allelic variants relate to ischemic stroke. We conducted a case-control study of 359 cases of ischemic stroke and 353 community controls. Participants were evaluated for known cerebrovascular risk factors, and the /"E-selectin"/ S128R and L554F genotypes were established using the polymerase chain reaction (PCR) method. The frequency of minor allele (R) and heterozygous (RS) genotype of /"E-selectin"/ S128R polymorphism was significantly higher in the /"stroke"/ patients than in the controls. Evaluation of genetic variation for /"E-selectin"/ L554F polymorphisms revealed that the frequency of minor allele (F) and its heterozygous genotype (LF) is almost 4 times higher in the /"stroke"/ patients than the controls (16.7 vs. 4.3 and 33.4 vs. 8.5, respectively). Multivariable logistic regression analysis after adjustment for age, sex and conventional vascular risk factors demonstrated that alleles R of S128R and F of L554F polymorphisms are independent risk factors for ischemic stroke. The combination of 2 minor alleles of /"E-selectin"/ genes appeared to be the strongest susceptibility factor for ischemic stroke (adjusted OR: 5.89, 95% CI: 2.84-12.21, p = 0.0001). Our study demonstrates that the /"E-selectin"/ S128R and L554F polymorphisms are associated with susceptibility to ischemic stroke. | [
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19420919 | E-selectin genetic variation as a susceptibility factor for ischemic stroke. | The polymorphism of the E-selectin gene has been implicated in the pathogenesis of atherosclerosis. We sought to explore whether the allelic variants relate to ischemic stroke. We conducted a case-control study of 359 cases of ischemic stroke and 353 community controls. Participants were evaluated for known cerebrovascular risk factors, and the E-selectin S128R and L554F genotypes were established using the polymerase chain reaction (PCR) method. The frequency of minor allele (R) and heterozygous (RS) genotype of E-selectin S128R polymorphism was significantly higher in the stroke patients than in the controls. Evaluation of genetic variation for E-selectin L554F polymorphisms revealed that the frequency of minor allele (F) and its heterozygous genotype (LF) is almost 4 times higher in the stroke patients than the controls (16.7 vs. 4.3 and 33.4 vs. 8.5, respectively). Multivariable logistic regression analysis after adjustment for age, sex and conventional vascular risk factors demonstrated that alleles R of S128R and F of L554F polymorphisms are independent risk factors for ischemic stroke. The combination of 2 minor alleles of E-selectin genes appeared to be the strongest susceptibility factor for ischemic stroke (adjusted OR: 5.89, 95% CI: 2.84-12.21, p = 0.0001). Our study demonstrates that the E-selectin S128R and L554F polymorphisms are associated with susceptibility to ischemic stroke. | /"E-selectin"/ genetic variation as a susceptibility factor for ischemic stroke. | The polymorphism of the /"E-selectin"/ gene has been implicated in the pathogenesis of /"atherosclerosis"/. We sought to explore whether the allelic variants relate to ischemic stroke. We conducted a case-control study of 359 cases of ischemic stroke and 353 community controls. Participants were evaluated for known cerebrovascular risk factors, and the /"E-selectin"/ S128R and L554F genotypes were established using the polymerase chain reaction (PCR) method. The frequency of minor allele (R) and heterozygous (RS) genotype of /"E-selectin"/ S128R polymorphism was significantly higher in the stroke patients than in the controls. Evaluation of genetic variation for /"E-selectin"/ L554F polymorphisms revealed that the frequency of minor allele (F) and its heterozygous genotype (LF) is almost 4 times higher in the stroke patients than the controls (16.7 vs. 4.3 and 33.4 vs. 8.5, respectively). Multivariable logistic regression analysis after adjustment for age, sex and conventional vascular risk factors demonstrated that alleles R of S128R and F of L554F polymorphisms are independent risk factors for ischemic stroke. The combination of 2 minor alleles of /"E-selectin"/ genes appeared to be the strongest susceptibility factor for ischemic stroke (adjusted OR: 5.89, 95% CI: 2.84-12.21, p = 0.0001). Our study demonstrates that the /"E-selectin"/ S128R and L554F polymorphisms are associated with susceptibility to ischemic stroke. | [
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19423162 | Risk of MDM2 SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia. | A single nucleotide polymorphism (SNP) in the promoter of MDM2 gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of MDM2, thereby causing an impairment of p53 tumor suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in cancer. To investigate whether that MDM2 SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to acute myeloid leukemia (AML), both polymorphisms were determined in a case-control study consisting of 231 AML patients and 128 normal individuals. The MDM2 SNP309G allele was associated with increased risk of AML. Furthermore, the p53 codon 72 and MDM2 SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and MDM2 polymorphisms were combined, no multiplicative joint effect between the MDM2 GG and p53 Pro/Pro genotypes exists in the risk of developing AML. These results suggest that the MDM2 SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML. | Risk of /"MDM2"/ SNP309 alone or in combination with the p53 codon 72 polymorphism in /"acute myeloid leukemia"/. | A single nucleotide polymorphism (SNP) in the promoter of /"MDM2"/ gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of /"MDM2"/, thereby causing an impairment of p53 tumor suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in cancer. To investigate whether that /"MDM2"/ SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to /"acute myeloid leukemia"/ (/"AML"/), both polymorphisms were determined in a case-control study consisting of 231 /"AML"/ patients and 128 normal individuals. The /"MDM2"/ SNP309G allele was associated with increased risk of /"AML"/. Furthermore, the p53 codon 72 and /"MDM2"/ SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and /"MDM2"/ polymorphisms were combined, no multiplicative joint effect between the /"MDM2"/ GG and p53 Pro/Pro genotypes exists in the risk of developing /"AML"/. These results suggest that the /"MDM2"/ SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of /"AML"/. | [
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19423162 | Risk of MDM2 SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia. | A single nucleotide polymorphism (SNP) in the promoter of MDM2 gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of MDM2, thereby causing an impairment of p53 tumor suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in cancer. To investigate whether that MDM2 SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to acute myeloid leukemia (AML), both polymorphisms were determined in a case-control study consisting of 231 AML patients and 128 normal individuals. The MDM2 SNP309G allele was associated with increased risk of AML. Furthermore, the p53 codon 72 and MDM2 SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and MDM2 polymorphisms were combined, no multiplicative joint effect between the MDM2 GG and p53 Pro/Pro genotypes exists in the risk of developing AML. These results suggest that the MDM2 SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML. | Risk of MDM2 SNP309 alone or in combination with the /"p53"/ codon 72 polymorphism in /"acute myeloid leukemia"/. | A single nucleotide polymorphism (SNP) in the promoter of MDM2 gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of MDM2, thereby causing an impairment of /"p53"/ tumor suppressor activity. A G-C exchange at /"p53"/ codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the /"p53"/ protein. Both polymorphisms have been implicated in cancer. To investigate whether that MDM2 SNP309 and /"p53"/ codon 72 polymorphism should be at least partially responsible for genetic susceptibility to /"acute myeloid leukemia"/ (/"AML"/), both polymorphisms were determined in a case-control study consisting of 231 /"AML"/ patients and 128 normal individuals. The MDM2 SNP309G allele was associated with increased risk of /"AML"/. Furthermore, the /"p53"/ codon 72 and MDM2 SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the /"p53"/ and MDM2 polymorphisms were combined, no multiplicative joint effect between the MDM2 GG and /"p53"/ Pro/Pro genotypes exists in the risk of developing /"AML"/. These results suggest that the MDM2 SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of /"AML"/. | [
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19423162 | Risk of MDM2 SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia. | A single nucleotide polymorphism (SNP) in the promoter of MDM2 gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of MDM2, thereby causing an impairment of p53 tumor suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in cancer. To investigate whether that MDM2 SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to acute myeloid leukemia (AML), both polymorphisms were determined in a case-control study consisting of 231 AML patients and 128 normal individuals. The MDM2 SNP309G allele was associated with increased risk of AML. Furthermore, the p53 codon 72 and MDM2 SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and MDM2 polymorphisms were combined, no multiplicative joint effect between the MDM2 GG and p53 Pro/Pro genotypes exists in the risk of developing AML. These results suggest that the MDM2 SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML. | Risk of /"MDM2"/ SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia. | A single nucleotide polymorphism (SNP) in the promoter of /"MDM2"/ gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of /"MDM2"/, thereby causing an impairment of p53 /"tumor"/ suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in /"cancer"/. To investigate whether that /"MDM2"/ SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to acute myeloid leukemia (AML), both polymorphisms were determined in a case-control study consisting of 231 AML patients and 128 normal individuals. The /"MDM2"/ SNP309G allele was associated with increased risk of AML. Furthermore, the p53 codon 72 and /"MDM2"/ SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and /"MDM2"/ polymorphisms were combined, no multiplicative joint effect between the /"MDM2"/ GG and p53 Pro/Pro genotypes exists in the risk of developing AML. These results suggest that the /"MDM2"/ SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML. | [
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19423162 | Risk of MDM2 SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia. | A single nucleotide polymorphism (SNP) in the promoter of MDM2 gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of MDM2, thereby causing an impairment of p53 tumor suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in cancer. To investigate whether that MDM2 SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to acute myeloid leukemia (AML), both polymorphisms were determined in a case-control study consisting of 231 AML patients and 128 normal individuals. The MDM2 SNP309G allele was associated with increased risk of AML. Furthermore, the p53 codon 72 and MDM2 SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and MDM2 polymorphisms were combined, no multiplicative joint effect between the MDM2 GG and p53 Pro/Pro genotypes exists in the risk of developing AML. These results suggest that the MDM2 SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML. | Risk of /"MDM2"/ SNP309 alone or in combination with the p53 codon 72 polymorphism in acute myeloid leukemia. | A single nucleotide polymorphism (SNP) in the promoter of /"MDM2"/ gene, SNP309 T>G (a T-G exchange at nucleotide 309 in the first intron), can increase the expression level of /"MDM2"/, thereby causing an impairment of p53 /"tumor"/ suppressor activity. A G-C exchange at p53 codon 72 polymorphism results in a substitution of proline (Pro) for arginine (Arg) in the transactivation domain, which was shown to alter the primary structure of the p53 protein. Both polymorphisms have been implicated in /"cancer"/. To investigate whether that /"MDM2"/ SNP309 and p53 codon 72 polymorphism should be at least partially responsible for genetic susceptibility to acute myeloid leukemia (AML), both polymorphisms were determined in a case-control study consisting of 231 AML patients and 128 normal individuals. The /"MDM2"/ SNP309G allele was associated with increased risk of AML. Furthermore, the p53 codon 72 and /"MDM2"/ SNP309 polymorphisms did not associate with age of onset and any other clinical parameters studied. When the p53 and /"MDM2"/ polymorphisms were combined, no multiplicative joint effect between the /"MDM2"/ GG and p53 Pro/Pro genotypes exists in the risk of developing AML. These results suggest that the /"MDM2"/ SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML. | [
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"text_name": "tumor"
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19429005 | Phactr2 and Parkinson's disease. | Attempts at replicating the first genome-wide association study (GWAS) in Parkinson's disease (PD) have not successfully identified genetic risk factors. The present study reevaluates data from the first GWAS and focuses on the SNP (rs11155313, located in the Phactr2 gene) with the lowest P-value in the Tier 2 patient-control series. We employed four case-control series to examine the nominated SNP rs11155313 and identified association in US (OR: 1.39, P=0.032), Canadian (OR: 1.41, P=0.014) and Irish (OR: 1.44, P=0.034) patient-control series, but not in the Norwegian series (OR: 1.15, P=0.27). When combining all four series the observed trend was statistically significant (OR: 1.30, P<0.001). This study shows that reappraisal of publicly available results of GWAS may help nominate new risk factors for PD. | /"Phactr2"/ and /"Parkinson's disease"/. | Attempts at replicating the first genome-wide association study (GWAS) in /"Parkinson's disease"/ (/"PD"/) have not successfully identified genetic risk factors. The present study reevaluates data from the first GWAS and focuses on the SNP (rs11155313, located in the /"Phactr2"/ gene) with the lowest P-value in the Tier 2 patient-control series. We employed four case-control series to examine the nominated SNP rs11155313 and identified association in US (OR: 1.39, P=0.032), Canadian (OR: 1.41, P=0.014) and Irish (OR: 1.44, P=0.034) patient-control series, but not in the Norwegian series (OR: 1.15, P=0.27). When combining all four series the observed trend was statistically significant (OR: 1.30, P<0.001). This study shows that reappraisal of publicly available results of GWAS may help nominate new risk factors for /"PD"/. | [
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19446452 | XRCC1 gene polymorphisms and breast cancer risk in different populations: a meta-analysis. | We performed a meta-analysis to investigate the role of XRCC1 polymorphisms Arg194Trp, Arg280His and Arg399Gln in breast cancer. The results were pooled in a manner that appropriately reflects a biological model of gene effect using a random effects logistic regression model without multiple comparisons. Forty studies from 31 reports were included with 10 465 cases and 10 888 controls at Arg194Trp, 6156 cases and 5806 controls at Arg280His, and 21 467 cases and 22 766 controls at Arg399Gln. Our analysis found a tendency towards a recessive effect of Arg280His variant in Asian population only (His/His vs. Arg/Arg+Arg/His: OR=2.27, 95% CI=0.82, 6.31). An increased breast cancer risk with a recessive effect was also suggested for Arg399Gln variant in Asian population (Gln/Gln vs. Arg/Arg+Arg/Gln: OR=1.59, 95% CI=1.22, 2.09) only. These findings suggest that polymorphisms Arg280His and Arg399Gln may modify breast cancer risk differently in Caucasian and Asian populations. | /"XRCC1"/ gene polymorphisms and /"breast cancer"/ risk in different populations: a meta-analysis. | We performed a meta-analysis to investigate the role of /"XRCC1"/ polymorphisms Arg194Trp, Arg280His and Arg399Gln in /"breast cancer"/. The results were pooled in a manner that appropriately reflects a biological model of gene effect using a random effects logistic regression model without multiple comparisons. Forty studies from 31 reports were included with 10 465 cases and 10 888 controls at Arg194Trp, 6156 cases and 5806 controls at Arg280His, and 21 467 cases and 22 766 controls at Arg399Gln. Our analysis found a tendency towards a recessive effect of Arg280His variant in Asian population only (His/His vs. Arg/Arg+Arg/His: OR=2.27, 95% CI=0.82, 6.31). An /"increased breast cancer"/ risk with a recessive effect was also suggested for Arg399Gln variant in Asian population (Gln/Gln vs. Arg/Arg+Arg/Gln: OR=1.59, 95% CI=1.22, 2.09) only. These findings suggest that polymorphisms Arg280His and Arg399Gln may modify /"breast cancer"/ risk differently in Caucasian and Asian populations. | [
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19450125 | UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. | AIMS: Variants in UGT1A1 have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of UGT1A1 variants in the prediction of severe diarrhea and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS _ METHODS: Genotyping of UGT1A1*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects. RESULTS: No association was found between UGT1A1*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of UGT1A1*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles. CONCLUSION: Our findings indicate that UGT1A1 genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea. | /"UGT1A1"/*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. | AIMS: Variants in /"UGT1A1"/ have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of /"UGT1A1"/ variants in the prediction of severe diarrhea and neutropenia in patients with /"colorectal cancer"/ receiving irinotecan in a routine clinical setting. MATERIALS _ METHODS: Genotyping of /"UGT1A1"/*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects. RESULTS: No association was found between /"UGT1A1"/*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of /"UGT1A1"/*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles. CONCLUSION: Our findings indicate that /"UGT1A1"/ genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea. | [
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19450125 | UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. | AIMS: Variants in UGT1A1 have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of UGT1A1 variants in the prediction of severe diarrhea and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS _ METHODS: Genotyping of UGT1A1*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects. RESULTS: No association was found between UGT1A1*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of UGT1A1*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles. CONCLUSION: Our findings indicate that UGT1A1 genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea. | /"UGT1A1"/*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. | AIMS: Variants in /"UGT1A1"/ have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of /"UGT1A1"/ variants in the prediction of severe /"diarrhea"/ and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS _ METHODS: Genotyping of /"UGT1A1"/*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects. RESULTS: No association was found between /"UGT1A1"/*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of /"UGT1A1"/*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of /"diarrhea"/ over all cycles. CONCLUSION: Our findings indicate that /"UGT1A1"/ genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe /"diarrhea"/. | [
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19450125 | UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. | AIMS: Variants in UGT1A1 have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of UGT1A1 variants in the prediction of severe diarrhea and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS _ METHODS: Genotyping of UGT1A1*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects. RESULTS: No association was found between UGT1A1*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of UGT1A1*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles. CONCLUSION: Our findings indicate that UGT1A1 genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea. | /"UGT1A1"/*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. | AIMS: Variants in /"UGT1A1"/ have previously been associated with /"toxicity"/ from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of /"UGT1A1"/ variants in the prediction of severe diarrhea and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS _ METHODS: Genotyping of /"UGT1A1"/*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and /"toxicity"/ for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 /"toxicity"/ occurred in 23% of subjects. RESULTS: No association was found between /"UGT1A1"/*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of /"UGT1A1"/*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles. CONCLUSION: Our findings indicate that /"UGT1A1"/ genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea. | [
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19450125 | UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. | AIMS: Variants in UGT1A1 have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of UGT1A1 variants in the prediction of severe diarrhea and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS _ METHODS: Genotyping of UGT1A1*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects. RESULTS: No association was found between UGT1A1*28 or c.-3156G>A and neutropenia. However, individuals carrying two copies of UGT1A1*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles. CONCLUSION: Our findings indicate that UGT1A1 genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea. | /"UGT1A1"/*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. | AIMS: Variants in /"UGT1A1"/ have previously been associated with toxicity from irinotecan chemotherapy. We conducted a pragmatic prospective cohort study to establish the relevance of /"UGT1A1"/ variants in the prediction of severe diarrhea and /"neutropenia"/ in patients with colorectal cancer receiving irinotecan in a routine clinical setting. MATERIALS _ METHODS: Genotyping of /"UGT1A1"/*28 and c.-3156G>A was undertaken in an unselected, prospective cohort of 96 individuals treated with irinotecan at a single major UK oncology centre. Data on cytotoxic drugs received, and toxicity for all irinotecan treatment cycles were collected from case notes. Over 95% (92/96) of patients received an intermediate dose of irinotecan (180 mg/m(2), twice weekly). Irinotecan was given in combination with other cytotoxic drugs in 93/96 subjects and Grade 3 or 4 toxicity occurred in 23% of subjects. RESULTS: No association was found between /"UGT1A1"/*28 or c.-3156G>A and /"neutropenia"/. However, individuals carrying two copies of /"UGT1A1"/*28 (p = 0.04; OR: 14; 95% CI: 1.1-185) or c.-3156G>A (p = 0.03) had a significantly increased risk of diarrhea over all cycles. CONCLUSION: Our findings indicate that /"UGT1A1"/ genotyping is not a good predictor of hematological toxicity in patients treated with intermediate irinotecan doses. However, it may be useful in the identification of patients at risk of severe diarrhea. | [
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19458483 | ERCC5 promoter polymorphisms at -763 and +25 predict the response to oxaliplatin-based chemotherapy in patients with advanced colorectal cancer. | This study aimed to investigate whether single nucleotide polymorphisms (SNPs) in the promoter of the excision repair cross complementation group 5 (ERCC5) gene influences response to oxaliplatin-based chemotherapy. Eighty-three patients with cytologically or histologically confirmed advanced colorectal cancer (CRC), at least one measurable lesion and underwent oxaliplatin-based chemotherapy were studied. To this end, six polymorphisms (-1415C>T, -763A>G, -413C>T, +25A>G, +202C>T, +372C>T) in the ERCC5 promoter were selected for investigation. Genomic DNA was obtained from peripheral blood cells, and polymerase chain reaction-ligation detection reaction was used to analyze these SNPs. The chi(2) test or Fisher's exact test was then used to investigate the association between polymorphisms and chemotherapy response. Our results showed that the response rate among patients with the -763GG genotype (72.7%) was significantly higher than that of other genotypes (22.2% for AA genotype, p = 0.008 and 37.2% for AG genotype, p = 0.046 respectively). In addition, the response rate among patients with the +25AA genotype (75%) was significantly higher than that of other genotypes (24.1% for GG genotype, p = 0.004 and 35.7% for AG genotype, p = 0.022 respectively). Patients with the -763A/+25G haplotype had a higher risk of non-response to oxaliplatin chemotherapy compared to those carrying the -763G/+25A haplotype (OR 2.672, 95% CI 1.353-5.278, p = 0.004). However, no genetic variation was observed at site -413, and no significant association was found between the -1415C>T, +202C>T or +372C>T polymorphisms and chemotherapy response. Therefore, these data suggest that ERCC5 promoter polymorphisms at -763 and +25 may be important predictors of response to oxaliplatin chemotherapy. | /"ERCC5"/ promoter polymorphisms at -763 and +25 predict the response to oxaliplatin-based chemotherapy in patients with advanced /"colorectal cancer"/. | This study aimed to investigate whether single nucleotide polymorphisms (SNPs) in the promoter of the /"excision repair cross complementation group 5"/ (/"ERCC5"/) gene influences response to oxaliplatin-based chemotherapy. Eighty-three patients with cytologically or histologically confirmed advanced /"colorectal cancer"/ (/"CRC"/), at least one measurable lesion and underwent oxaliplatin-based chemotherapy were studied. To this end, six polymorphisms (-1415C>T, -763A>G, -413C>T, +25A>G, +202C>T, +372C>T) in the /"ERCC5"/ promoter were selected for investigation. Genomic DNA was obtained from peripheral blood cells, and polymerase chain reaction-ligation detection reaction was used to analyze these SNPs. The chi(2) test or Fisher's exact test was then used to investigate the association between polymorphisms and chemotherapy response. Our results showed that the response rate among patients with the -763GG genotype (72.7%) was significantly higher than that of other genotypes (22.2% for AA genotype, p = 0.008 and 37.2% for AG genotype, p = 0.046 respectively). In addition, the response rate among patients with the +25AA genotype (75%) was significantly higher than that of other genotypes (24.1% for GG genotype, p = 0.004 and 35.7% for AG genotype, p = 0.022 respectively). Patients with the -763A/+25G haplotype had a higher risk of non-response to oxaliplatin chemotherapy compared to those carrying the -763G/+25A haplotype (OR 2.672, 95% CI 1.353-5.278, p = 0.004). However, no genetic variation was observed at site -413, and no significant association was found between the -1415C>T, +202C>T or +372C>T polymorphisms and chemotherapy response. Therefore, these data suggest that /"ERCC5"/ promoter polymorphisms at -763 and +25 may be important predictors of response to oxaliplatin chemotherapy. | [
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19470260 | [Correlation between ABO blood type gene and attention-deficit hyperactivity disorder in children]. | OBJECTIVE: To investigate the correlation between ABO blood type gene and attention-deficit hyperactivity disorder (ADHD) in children. METHODS: ABO blood types were determined using glass sheet method in 96 children with ADHD and their parents. O gene was identified using polymerase chain reaction and restriction fragment length polymorphism in patients with A or B blood type. Haplotype-based haplotype relative risk (HHRR), transmission-disequilibrium test (TDT) and Chi-square test were used to examine the association between ABO gene and ADHD. RESULTS: TDT results showed significant differences in the allele of ABO between the 96 children with ADHD and within-family controls (chi2=6.017, df=2, P< 0.05). Chi-square test results showed differences in the allele of A and B (chi2=3.289, df=1, P=0.07) as well as O and B (chi2=3.629, df=1, P=0.057 ) between ADHD children and within-family controls. The frequencies of O and A genes were higher than that of B gene in ADHD children. CONCLUSIONS: There was correlation between ABO blood type gene and ADHD in children. The risk of ADHD is increased in the presence of alleles O and A, but the risk is reduced in the presence of allele B. | [Correlation between /"ABO"/ blood type gene and /"attention-deficit hyperactivity disorder"/ in children]. | OBJECTIVE: To investigate the correlation between /"ABO"/ blood type gene and /"attention-deficit hyperactivity disorder"/ (/"ADHD"/) in children. METHODS: /"ABO"/ blood types were determined using glass sheet method in 96 children with /"ADHD"/ and their parents. O gene was identified using polymerase chain reaction and restriction fragment length polymorphism in patients with A or B blood type. Haplotype-based haplotype relative risk (HHRR), transmission-disequilibrium test (TDT) and Chi-square test were used to examine the association between /"ABO"/ gene and /"ADHD"/. RESULTS: TDT results showed significant differences in the allele of /"ABO"/ between the 96 children with /"ADHD"/ and within-family controls (chi2=6.017, df=2, P< 0.05). Chi-square test results showed differences in the allele of A and B (chi2=3.289, df=1, P=0.07) as well as O and B (chi2=3.629, df=1, P=0.057 ) between /"ADHD"/ children and within-family controls. The frequencies of O and A genes were higher than that of B gene in /"ADHD"/ children. CONCLUSIONS: There was correlation between /"ABO"/ blood type gene and /"ADHD"/ in children. The risk of /"ADHD"/ is increased in the presence of alleles O and A, but the risk is reduced in the presence of allele B. | [
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19478460 | Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia. | Genetic variants of the SLC6A3 gene that encodes the human dopamine transporter (DAT) have been linked to a variety of neuropsychiatric disorders, particularly attention deficit hyperactivity disorder. In addition, the homozygous Slc6a3 knockout mouse displays a hyperactivity phenotype. Here, we analyzed 2 unrelated consanguineous families with infantile parkinsonism-dystonia (IPD) syndrome and identified homozygous missense SLC6A3 mutations (p.L368Q and p.P395L) in both families. Functional studies demonstrated that both mutations were loss-of-function mutations that severely reduced levels of mature (85-kDa) DAT while having a differential effect on the apparent binding affinity of dopamine. Thus, in humans, loss-of-function SLC6A3 mutations that impair DAT-mediated dopamine transport activity are associated with an early-onset complex movement disorder. Identification of the molecular basis of IPD suggests SLC6A3 as a candidate susceptibility gene for other movement disorders associated with parkinsonism and/or dystonic features. | Homozygous loss-of-function mutations in the gene encoding the /"dopamine transporter"/ are associated with infantile /"parkinsonism-dystonia"/. | Genetic variants of the /"SLC6A3"/ gene that encodes the human /"dopamine transporter"/ (/"DAT"/) have been linked to a variety of neuropsychiatric disorders, particularly attention deficit hyperactivity disorder. In addition, the homozygous /"Slc6a3"/ knockout mouse displays a hyperactivity phenotype. Here, we analyzed 2 unrelated consanguineous families with infantile /"parkinsonism-dystonia (IPD) syndrome"/ and identified homozygous missense /"SLC6A3"/ mutations (p.L368Q and p.P395L) in both families. Functional studies demonstrated that both mutations were loss-of-function mutations that severely reduced levels of mature (85-kDa) /"DAT"/ while having a differential effect on the apparent binding affinity of dopamine. Thus, in humans, loss-of-function /"SLC6A3"/ mutations that impair /"DAT"/-mediated dopamine transport activity are associated with an early-onset complex movement disorder. Identification of the molecular basis of IPD suggests /"SLC6A3"/ as a candidate susceptibility gene for other movement disorders associated with parkinsonism and/or dystonic features. | [
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19478460 | Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia. | Genetic variants of the SLC6A3 gene that encodes the human dopamine transporter (DAT) have been linked to a variety of neuropsychiatric disorders, particularly attention deficit hyperactivity disorder. In addition, the homozygous Slc6a3 knockout mouse displays a hyperactivity phenotype. Here, we analyzed 2 unrelated consanguineous families with infantile parkinsonism-dystonia (IPD) syndrome and identified homozygous missense SLC6A3 mutations (p.L368Q and p.P395L) in both families. Functional studies demonstrated that both mutations were loss-of-function mutations that severely reduced levels of mature (85-kDa) DAT while having a differential effect on the apparent binding affinity of dopamine. Thus, in humans, loss-of-function SLC6A3 mutations that impair DAT-mediated dopamine transport activity are associated with an early-onset complex movement disorder. Identification of the molecular basis of IPD suggests SLC6A3 as a candidate susceptibility gene for other movement disorders associated with parkinsonism and/or dystonic features. | Homozygous loss-of-function mutations in the gene encoding the /"dopamine transporter"/ are associated with infantile parkinsonism-dystonia. | Genetic variants of the /"SLC6A3"/ gene that encodes the human /"dopamine transporter"/ (/"DAT"/) have been linked to a variety of /"neuropsychiatric disorders"/, particularly attention deficit hyperactivity disorder. In addition, the homozygous /"Slc6a3"/ knockout mouse displays a hyperactivity phenotype. Here, we analyzed 2 unrelated consanguineous families with infantile parkinsonism-dystonia (IPD) syndrome and identified homozygous missense /"SLC6A3"/ mutations (p.L368Q and p.P395L) in both families. Functional studies demonstrated that both mutations were loss-of-function mutations that severely reduced levels of mature (85-kDa) /"DAT"/ while having a differential effect on the apparent binding affinity of dopamine. Thus, in humans, loss-of-function /"SLC6A3"/ mutations that impair /"DAT"/-mediated dopamine transport activity are associated with an early-onset complex movement disorder. Identification of the molecular basis of IPD suggests /"SLC6A3"/ as a candidate susceptibility gene for other movement disorders associated with parkinsonism and/or dystonic features. | [
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19484476 | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings. | Polymorphisms in /"BRCA1"/, /"BRCA1"/-interacting genes and susceptibility of /"breast cancer"/ in Chinese women. | PURPOSE: /"BRCA1"/-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with /"BRCA1"/ in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' /"breast cancer"/ susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and /"BRCA1"/ and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 /"breast cancer"/ cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased /"breast cancer"/ risk among subjects carrying variant homozygote of /"BRCA1"/ rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: /"BRCA1"/ and ZNF350 may jointly contribute to individuals' susceptibility of /"breast cancer"/ in Chinese women. Further functional studies are warranted to validate our findings. | [
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19484476 | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings. | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of /"breast cancer"/ in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (/"BRIP1"/) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' /"breast cancer"/ susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of /"BRIP1"/, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 /"breast cancer"/ cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased /"breast cancer"/ risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of /"breast cancer"/ in Chinese women. Further functional studies are warranted to validate our findings. | [
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19484476 | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings. | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of /"breast cancer"/ in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and /"zinc finger protein 350"/ (/"ZNF350"/) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' /"breast cancer"/ susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, /"ZNF350"/ and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 /"breast cancer"/ cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of /"ZNF350"/ conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of /"ZNF350"/ polymorphisms accounted for increased /"breast cancer"/ risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for /"ZNF350"/ rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and /"ZNF350"/ may jointly contribute to individuals' susceptibility of /"breast cancer"/ in Chinese women. Further functional studies are warranted to validate our findings. | [
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19484476 | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings. | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of /"breast cancer"/ in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal /"helicase 1"/ (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' /"breast cancer"/ susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 /"breast cancer"/ cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased /"breast cancer"/ risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of /"breast cancer"/ in Chinese women. Further functional studies are warranted to validate our findings. | [
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19484476 | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings. | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and /"zinc finger protein 350"/ (/"ZNF350"/) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes /"may jointly"/ affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, /"ZNF350"/ and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of /"ZNF350"/ conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of /"ZNF350"/ polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for /"ZNF350"/ rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and /"ZNF350"/ /"may jointly"/ contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings. | [
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19484476 | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and zinc finger protein 350 (ZNF350) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes may jointly affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, ZNF350 and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of ZNF350 conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of ZNF350 polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for ZNF350 rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and ZNF350 may jointly contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings. | Polymorphisms in BRCA1, BRCA1-interacting genes and susceptibility of breast cancer in Chinese women. | PURPOSE: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) and /"zinc finger protein 350"/ (/"ZNF350"/) work with BRCA1 in tumor suppression procedures. Low penetrance variants of these three genes /"may jointly"/ affect individuals' breast cancer susceptibility in general population. METHODS: We focused on potentially functional single nucleotide polymorphisms (SNPs) in the coding regions of BRIP1, /"ZNF350"/ and BRCA1 and pairwise-tagging approach was used to minimize the number of SNPs. Five SNPs were selected and genotyped by PCR-restriction fraction length polymorphism or PCR-primer introduced restriction analysis assays in a case-control study with 568 breast cancer cases and 624 controls in a Chinese population. RESULTS: All of the five SNPs except rs2278415 of /"ZNF350"/ conferred a modestly increased risk, although, with no statistical significance. Joint effect analyses indicated that all the variant genotypes of /"ZNF350"/ polymorphisms accounted for increased breast cancer risk among subjects carrying variant homozygote of BRCA1 rs799917, particularly for /"ZNF350"/ rs4986773 (OR = 2.03, 95%CI = 1.02-4.05, the test for gene-gene interaction P (int) = 0.059). CONCLUSION: BRCA1 and /"ZNF350"/ /"may jointly"/ contribute to individuals' susceptibility of breast cancer in Chinese women. Further functional studies are warranted to validate our findings. | [
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19495527 | MECP2 mutations in Malaysian Rett syndrome patients. | INTRODUCTION: Rett syndrome (RS) is a severe neurodevelopmental disorder characterised by normal neurological development followed by progressive developmental regression. The X-linked dominant inheritance of RS has been mapped to the gene that encodes the methyl-CpG-binding protein-2 (MECP2) at Xq28. In the present study, denaturing high-performance liquid chromatography (DHPLC) was used to detect mutations in the MECP2 gene in 20 Malaysian RS patients. METHODS: Polymerase chain reaction (PCR) was carried out to amplify the MECP2 coding exons 2, 3, and 4 in a total of eight reactions (exons 2, 3a, 3b, 4a, 4b, 4c, 4d and 4e). Subsequently, PCR products were analysed by DHPLC. RESULTS: Mutations in the MECP2 gene were detected in 13 of the 20 (65 percent) RS patients. 11 patients had mutations in exons 3b and 4a and six patients had mutations in exon 4c. These mutations were mainly concentrated in the methyl-CpG-binding domain and the transcriptional-repression domain. CONCLUSION: Through the use of post-PCR high-performance liquid chromatography, 65 percent of 20 RS patients were found to have mutation(s) in the MECP2. | /"MECP2"/ mutations in Malaysian /"Rett syndrome"/ patients. | INTRODUCTION: /"Rett syndrome"/ (/"RS"/) is a severe neurodevelopmental disorder characterised by normal neurological development followed by progressive developmental regression. The X-linked dominant inheritance of /"RS"/ has been mapped to the gene that encodes the /"methyl-CpG-binding protein-2"/ (/"MECP2"/) at Xq28. In the present study, denaturing high-performance liquid chromatography (DHPLC) was used to detect mutations in the /"MECP2"/ gene in 20 Malaysian /"RS"/ patients. METHODS: Polymerase chain reaction (PCR) was carried out to amplify the /"MECP2"/ coding exons 2, 3, and 4 in a total of eight reactions (exons 2, 3a, 3b, 4a, 4b, 4c, 4d and 4e). Subsequently, PCR products were analysed by DHPLC. RESULTS: Mutations in the /"MECP2"/ gene were detected in 13 of the 20 (65 percent) /"RS"/ patients. 11 patients had mutations in exons 3b and 4a and six patients had mutations in exon 4c. These mutations were mainly concentrated in the methyl-CpG-binding domain and the transcriptional-repression domain. CONCLUSION: Through the use of post-PCR high-performance liquid chromatography, 65 percent of 20 /"RS"/ patients were found to have mutation(s) in the /"MECP2"/. | [
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19495527 | MECP2 mutations in Malaysian Rett syndrome patients. | INTRODUCTION: Rett syndrome (RS) is a severe neurodevelopmental disorder characterised by normal neurological development followed by progressive developmental regression. The X-linked dominant inheritance of RS has been mapped to the gene that encodes the methyl-CpG-binding protein-2 (MECP2) at Xq28. In the present study, denaturing high-performance liquid chromatography (DHPLC) was used to detect mutations in the MECP2 gene in 20 Malaysian RS patients. METHODS: Polymerase chain reaction (PCR) was carried out to amplify the MECP2 coding exons 2, 3, and 4 in a total of eight reactions (exons 2, 3a, 3b, 4a, 4b, 4c, 4d and 4e). Subsequently, PCR products were analysed by DHPLC. RESULTS: Mutations in the MECP2 gene were detected in 13 of the 20 (65 percent) RS patients. 11 patients had mutations in exons 3b and 4a and six patients had mutations in exon 4c. These mutations were mainly concentrated in the methyl-CpG-binding domain and the transcriptional-repression domain. CONCLUSION: Through the use of post-PCR high-performance liquid chromatography, 65 percent of 20 RS patients were found to have mutation(s) in the MECP2. | /"MECP2"/ mutations in Malaysian Rett syndrome patients. | INTRODUCTION: Rett syndrome (RS) is a severe /"neurodevelopmental disorder"/ characterised by normal neurological development followed by progressive developmental regression. The X-linked dominant inheritance of RS has been mapped to the gene that encodes the /"methyl-CpG-binding protein-2"/ (/"MECP2"/) at Xq28. In the present study, denaturing high-performance liquid chromatography (DHPLC) was used to detect mutations in the /"MECP2"/ gene in 20 Malaysian RS patients. METHODS: Polymerase chain reaction (PCR) was carried out to amplify the /"MECP2"/ coding exons 2, 3, and 4 in a total of eight reactions (exons 2, 3a, 3b, 4a, 4b, 4c, 4d and 4e). Subsequently, PCR products were analysed by DHPLC. RESULTS: Mutations in the /"MECP2"/ gene were detected in 13 of the 20 (65 percent) RS patients. 11 patients had mutations in exons 3b and 4a and six patients had mutations in exon 4c. These mutations were mainly concentrated in the methyl-CpG-binding domain and the transcriptional-repression domain. CONCLUSION: Through the use of post-PCR high-performance liquid chromatography, 65 percent of 20 RS patients were found to have mutation(s) in the /"MECP2"/. | [
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19509271 | Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma. | Gene expression profiling has revealed that the gene coding for cannabinoid receptor 1 (CB1) is highly up-regulated in rhabdomyosarcoma biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Delta(9)-tetrahydrocannabinol lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA-mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma. | /"Cannabinoid receptor 1"/ is a potential drug target for treatment of translocation-positive /"rhabdomyosarcoma"/. | Gene expression profiling has revealed that the gene coding for /"cannabinoid receptor 1"/ (/"CB1"/) is highly up-regulated in /"rhabdomyosarcoma"/ biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether /"CB1"/ is a potential drug target in /"rhabdomyosarcoma"/. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Delta(9)-tetrahydrocannabinol lowers the viability of translocation-positive /"rhabdomyosarcoma"/ cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA-mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive /"rhabdomyosarcoma"/. | [
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19509271 | Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma. | Gene expression profiling has revealed that the gene coding for cannabinoid receptor 1 (CB1) is highly up-regulated in rhabdomyosarcoma biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Delta(9)-tetrahydrocannabinol lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA-mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma. | /"Cannabinoid receptor 1"/ is a potential drug target for treatment of translocation-positive rhabdomyosarcoma. | Gene expression profiling has revealed that the gene coding for /"cannabinoid receptor 1"/ (/"CB1"/) is highly up-regulated in rhabdomyosarcoma biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, /"breast cancer"/, and melanoma, we evaluated whether /"CB1"/ is a potential drug target in rhabdomyosarcoma. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Delta(9)-tetrahydrocannabinol lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA-mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma. | [
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19523860 | The role of TP53 PRO47SER and ARG72PRO single nucleotide polymorphisms in the susceptibility to bladder cancer. | Several studies have investigated the association between TP53 Arg72Pro and an increased risk of developing bladder tumors, with controversial results. Taking advantage of the high admixture rates in the Brazilian population, we genotyped 94 bladder cancer patients (76 males and 18 females; aged 21-96 years old; 67 13 years old; 79 smokers and 15 nonsmokers) carefully paired with 159 controls (104 males and 55 females; aged 20-100 years old; 65 21 years old; 126 smokers and 33 nonsmokers) with respect to environmental exposure, diet routine, lifetime occupational history, smoking history, general health conditions, and previous diseases. Arg/Pro genotype was under-represented in the patient population, and conferred a 44% lower risk of bladder cancer. Univariate logistic regression analysis also identified male sex (OR=6.87, 95% CI=3.78-12.50; P<0.001), age over 65 years (OR=4.44, 95% CI=2.56-7.71; P<0.001), and smoking habits (OR=18.61, 95% CI=9.62-36.03; P<0.001) as important risk factors for bladder cancer. However, the TP53Arg72Pro genotype disappeared as a susceptibility factor both in the multivariate regression analysis and in a univariate regression analysis adjusted for gender, age, and smoking, suggesting that it was connected with one of these factors in the predisposition to bladder cancer. Indeed, a further analysis demonstrated that both alleles and genotype variants of TP53Arg72Pro are less frequent in older patients (P=0.029). We concluded that the effect of TP53Arg72Pro, described in some studies as an important risk factor, may not be an independent, but an age-related factor of susceptibility to bladder cancer. | The role of /"TP53"/ PRO47SER and ARG72PRO single nucleotide polymorphisms in the susceptibility to /"bladder cancer"/. | Several studies have investigated the association between /"TP53"/ Arg72Pro and an increased risk of developing /"bladder tumors"/, with controversial results. Taking advantage of the high admixture rates in the Brazilian population, we genotyped 94 /"bladder cancer"/ patients (76 males and 18 females; aged 21-96 years old; 67 13 years old; 79 smokers and 15 nonsmokers) carefully paired with 159 controls (104 males and 55 females; aged 20-100 years old; 65 21 years old; 126 smokers and 33 nonsmokers) with respect to environmental exposure, diet routine, lifetime occupational history, smoking history, general health conditions, and previous diseases. Arg/Pro genotype was under-represented in the patient population, and conferred a 44% lower risk of /"bladder cancer"/. Univariate logistic regression analysis also identified male sex (OR=6.87, 95% CI=3.78-12.50; P<0.001), age over 65 years (OR=4.44, 95% CI=2.56-7.71; P<0.001), and smoking habits (OR=18.61, 95% CI=9.62-36.03; P<0.001) as important risk factors for /"bladder cancer"/. However, the /"TP53"/Arg72Pro genotype disappeared as a susceptibility factor both in the multivariate regression analysis and in a univariate regression analysis adjusted for gender, age, and smoking, suggesting that it was connected with one of these factors in the predisposition to /"bladder cancer"/. Indeed, a further analysis demonstrated that both alleles and genotype variants of /"TP53"/Arg72Pro are less frequent in older patients (P=0.029). We concluded that the effect of /"TP53"/Arg72Pro, described in some studies as an important risk factor, may not be an independent, but an age-related factor of susceptibility to /"bladder cancer"/. | [
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