Association of trypanolytic ApoL1 variants with kidney disease in African Americans

Science. 2010 Aug 13;329(5993):841-5. doi: 10.1126/science.1193032.

Giulio Genovese ¹, David J Friedman, Michael D Ross, Laurence Lecordier, Pierrick Uzureau, Barry I Freedman, Donald W Bowden, Carl D Langefeld, Taras K Oleksyk, Andrea L Uscinski Knob, Andrea J Bernhardy, Pamela J Hicks, George W Nelson, Benoit Vanhollebeke, Cheryl A Winkler, Jeffrey B Kopp, Etienne Pays, Martin R Pollak

Affiliations

Affiliation

1 Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

PMID: 20647424 DOI: 10.1126/science.1193032

Abstract

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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