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Association of trypanolytic ApoL1 variants with kidney disease in African Americans.

Genovese, Giulio; Friedman, David J; Ross, Michael D; Lecordier, Laurence; Uzureau, Pierrick; Freedman, Barry I; Bowden, Donald W; Langefeld, Carl D; Oleksyk, Taras K; Uscinski Knob, Andrea L; Bernhardy, Andrea J; Hicks, Pamela J; Nelson, George W; Vanhollebeke, Benoit; Winkler, Cheryl A; Kopp, Jeffrey B; Pays, Etienne; Pollak, Martin R.
Science; 329(5993): 841-5, 2010 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-20647424
African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.
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