| Literature DB >> 18794856 |
Jeffrey B Kopp1, Michael W Smith, George W Nelson, Randall C Johnson, Barry I Freedman, Donald W Bowden, Taras Oleksyk, Louise M McKenzie, Hiroshi Kajiyama, Tejinder S Ahuja, Jeffrey S Berns, William Briggs, Monique E Cho, Richard A Dart, Paul L Kimmel, Stephen M Korbet, Donna M Michel, Michele H Mokrzycki, Jeffrey R Schelling, Eric Simon, Howard Trachtman, David Vlahov, Cheryl A Winkler.
Abstract
The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.Entities:
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Year: 2008 PMID： 18794856 PMCID： PMC2827354 DOI： 10.1038/ng.226
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330