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Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy
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نویسنده
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stark k. ,esslinger u.b. ,reinhard w. ,petrov g. ,winkler t. ,komajda m. ,isnard r. ,charron p. ,villard e. ,cambien f. ,tiret l. ,aumont m.-c. ,dubourg o. ,trochu j.-n. ,fauchier l. ,degroote p. ,richter a. ,maisch b. ,wichter t. ,zollbrecht c. ,grassl m. ,schunkert h. ,linsel-nitschke p. ,erdmann j. ,baumert j. ,illig t. ,klopp n. ,wichmann h.-e. ,meisinger c. ,koenig w. ,lichtner p. ,meitinger t. ,schillert a. ,könig i.r. ,hetzer r. ,heid i.m. ,regitz-zagrosek v. ,hengstenberg c.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 10 - صفحه:1 -9
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چکیده
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Dilated cardiomyopathy (dcm) is a structural heart disease with strong genetic background. monogenic forms of dcm are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. however,strong evidence suggests that genetic factors also affect the susceptibility to idiopathic dcm. to identify risk alleles for non-familial forms of dcm,we carried out a case-control association study,genotyping 664 dcm cases and 1,874 population-based healthy controls from germany using a 50k human cardiovascular disease bead chip covering more than 2,000 genes preselected for cardiovascular relevance. after quality control,30,920 single nucleotide polymorphisms (snp) were tested for association with the disease by logistic regression adjusted for gender,and results were genomic-control corrected. the analysis revealed a significant association between a snp in hspb7 gene (rs1739843,minor allele frequency 39%) and idiopathic dcm (p = 1.06×10-6,or = 0.67 [95% ci 0.57-0.79] for the minor allele t). three more snps showed p < 2.21×10-5. de novo genotyping of these four snps was done in three independent case-control studies of idiopathic dcm. association between snp rs1739843 and dcm was significant in all replication samples: germany (n = 564,n = 981 controls,p = 2.07×10-3,or = 0.79 [95% ci 0.67-0.92]),france 1 (n = 433 cases,n = 395 controls,p = 3.73×10-3,or = 0.74 [95% ci 0.60-0.91]),and france 2 (n = 249 cases,n = 380 controls,p = 2.26×10-4,or = 0.63 [95% ci 0.50-0.81]). the combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic dcm (p = 5.28×10-13,or = 0.72 [95% ci 0.65-0.78]). none of the other three snps showed significant results in the replication stage. this finding of the hspb7 gene from a genetic search for idiopathic dcm using a large snp panel underscores the influence of common polymorphisms on dcm susceptibility. copyright: © 2010 stark et al.
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آدرس
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klinik und poliklinik für innere medizin ii,universitätsklinikum regensburg,regensburg, Germany, klinik und poliklinik für innere medizin ii,universitätsklinikum regensburg,regensburg, Germany, klinik und poliklinik für innere medizin ii,universitätsklinikum regensburg,regensburg, Germany, institute for gender in medicine,center for cardiovascular research,charité campus mitte,berlin,germany,department of cardiothoracic and vascular surgery,german heart institute berlin,berlin, Germany, institute of epidemiology,public health,and gender studies,university of regensburg,regensburg, Germany, institut national de la santé et de la recherche médicale (inserm) umr-s956,university pierre et marie curie (paris 6),institut de cardiologie,departement de génétique,ap-hp,hôpital pitié-salpêtrière,paris, France, institut national de la santé et de la recherche médicale (inserm) umr-s956,university pierre et marie curie (paris 6),institut de cardiologie,departement de génétique,ap-hp,hôpital pitié-salpêtrière,paris, France, institut national de la santé et de la recherche médicale (inserm) umr-s956,university pierre et marie curie (paris 6),institut de cardiologie,departement de génétique,ap-hp,hôpital pitié-salpêtrière,paris, France, institut national de la santé et de la recherche médicale (inserm) umr-s956,university pierre et marie curie (paris 6),institut de cardiologie,departement de génétique,ap-hp,hôpital pitié-salpêtrière,paris, France, institut national de la santé et de la recherche médicale (inserm),umr-s937,university pierre et marie curie (paris 6),paris, France, institut national de la santé et de la recherche médicale (inserm),umr-s937,university pierre et marie curie (paris 6),paris, France, service de cardiologie,hôpital bichat,ap-hp,paris, France, service de cardiologie,université de versailles-saint quentin,hôpital ambroise paré,ap-hp,boulogne, France, service de cardiologie,hôpital laennec,nantes, France, service de cardiologie b et laboratoire d'electrophysiologie cardiaque,pole coeur thorax vasculaire hémostase,centre hospitalier universitaire trousseau,tours, France, service de cardiologie,hôpital cardiologique,lille, France, klinik für innere medizin i - kardiologie,philipps-universität marburg,marburg, Germany, klinik für innere medizin i - kardiologie,philipps-universität marburg,marburg, Germany, medizinische klinik und poliklinik c,kardiologie und angiologie,universitätsklinikum münster,münster, Germany, klinik und poliklinik für innere medizin ii,universitätsklinikum regensburg,regensburg, Germany, klinik und poliklinik für innere medizin ii,universitätsklinikum regensburg,regensburg, Germany, medizinische klinik ii,universität zu lübeck,lübeck, Germany, medizinische klinik ii,universität zu lübeck,lübeck, Germany, medizinische klinik ii,universität zu lübeck,lübeck, Germany, institute of epidemiology,helmholtzzentrum münchen,münchen-neuherberg, Germany, institute of epidemiology,helmholtzzentrum münchen,münchen-neuherberg, Germany, institute of epidemiology,helmholtzzentrum münchen,münchen-neuherberg, Germany, institute of epidemiology,helmholtzzentrum münchen,münchen-neuherberg, Germany, institute of epidemiology,helmholtzzentrum münchen,münchen-neuherberg,germany,central hospital of augsburg,monica/kora myocardial infarction registry,augsburg, Germany, department of internal medicine ii - cardiology,university of ulm medical center,ulm, Germany, institute of human genetics,helmholtzzentrum münchen,münchen-neuherberg, Germany, institute of human genetics,helmholtzzentrum münchen,münchen-neuherberg,germany,institute of human genetics,klinikum rechts der isar,technische universität münchen,münchen, Germany, institute of medical biometry and statistics,university of lübeck,lübeck, Germany, institute of medical biometry and statistics,university of lübeck,lübeck, Germany, department of cardiothoracic and vascular surgery,german heart institute berlin,berlin, Germany, institute of epidemiology,public health,and gender studies,university of regensburg,regensburg,germany,institute of epidemiology,helmholtzzentrum münchen,münchen-neuherberg, Germany, institute for gender in medicine,center for cardiovascular research,charité campus mitte,berlin, Germany, klinik und poliklinik für innere medizin ii,universitätsklinikum regensburg,regensburg, Germany
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Authors
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