MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis by Kopp Jeffrey B, Smith Michael W, Nelson George W, Johnson Randall C, Freedman Barry I, Bowden Donald W, Oleksyk Taras, McKenzie Louise M, Kajiyama Hiroshi, Ahuja Tejinder S, Berns Jeffrey S, Briggs William, Cho Monique E, Dart Richard A, Kimmel Paul L, Korbet Stephen M, Michel Donna M, Mokrzycki Michele H, Schelling Jeffrey R, Simon Eric, Trachtman Howard, Vlahov David, Winkler Cheryl A in Nature genetics (2008).

[PMID: 18794856] PubMed


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.

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