Villard, Eric and Perret, Claire and Gary, Francoise and Proust, Carole and Dilanian, Gilles and Hengstenberg, Christian and Ruppert, Volker and Arbustini, Eloisa and Wichter, Thomas and Germain, Marine and Dubourg, Olivier and Tavazzi, Luigi and Aumont, Marie-Claude and DeGroote, Pascal and Fauchier, Laurent and Trochu, Jean-Noel and Gibelin, Pierre and Aupetit, Jean-Francois and Stark, Klaus and Erdmann, Jeanette and Hetzer, Roland and Roberts, Angharad M. and Barton, Paul J. R. and Regitz-Zagrosek, Vera and Aslam, Uzma and Duboscq-Bidot, Laetitia and Meyborg, Matthias and Maisch, Bernhard and Madeira, Hugo and Waldenstrom, Anders and Galve, Enrique and Cleland, John G. and Dorent, Richard and Roizes, Gerard and Zeller, Tanja and Blankenberg, Stefan and Goodall, Alison H. and Cook, Stuart and Tregouet, David A. and Tiret, Laurence and Isnard, Richard and Komajda, Michel and Charron, Philippe and Cambien, Francois (2011) A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy. EUROPEAN HEART JOURNAL, 32 (9). pp. 1065-1076. ISSN 0195-668X,
Full text not available from this repository. (Request a copy)Abstract
Aims Dilated cardiomyopathy (DCM) is a major cause of heart failure with a high familial recurrence risk. So far, the genetics of DCM remains largely unresolved. We conducted the first genome-wide association study (GWAS) to identify loci contributing to sporadic DCM. Methods and results One thousand one hundred and seventy-nine DCM patients and 1108 controls contributed to the discovery phase. Pools of DNA stratified on disease status, population, age, and gender were constituted and used for testing association of DCM with 517 382 single nucleotide polymorphisms (SNPs). Three DCM-associated SNPs were confirmed by individual genotyping (P<5.0 10(-7)), and two of them, rs10927875 and rs2234962, were replicated in independent samples (1165 DCM patients and 1302 controls), with P-values of 0.002 and 0.009, respectively. rs10927875 maps to a region on chromosome 1p36.13 which encompasses several genes among which HSPB7 has been formerly suggested to be implicated in DCM. The second identified locus involves rs2234962, a non-synonymous SNP (c.T757C, p.C151R) located within the sequence of BAG3 on chromosome 10q26. To assess whether coding mutations of BAG3 might cause monogenic forms of the disease, we sequenced BAG3 exons in 168 independent index cases diagnosed with familial DCM and identified four truncating and two missense mutations. Each mutation was heterozygous, present in all genotyped relatives affected by the disease and absent in a control group of 347 healthy individuals, strongly suggesting that these mutations are causing the disease. Conclusion This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CANDIDATE GENES; RISK; BAG3; VARIANTS; COMMON; POPULATIONS; MUTATION; DISEASES; CLCNKA; DNA; Dilated cardiomyopathy; Heart failure; Genome wide association study; CLCNKA; HSPB7; BAG3 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jun 2020 08:36 |
| Last Modified: | 18 Jun 2020 08:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20877 |
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