Journal
SCIENCE
Volume 329, Issue 5993, Pages 841-845Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1193032
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Funding
- Walloon Region
- Fonds National de la Recherche Scientifique
- Belgian Science Policy
- NIH [R01 DK54931, K08-DK076868, R01 DK066358, R01 DK053591, R01 HL56266, R01 DK 070941, R01 DK 084149]
- National Institute of Diabetes, Digestive, and Kidney Disease [Z01 DK043308]
- NCI, Center for Cancer Research [ZIA BC 010022]
- NephCure Foundation
- NCI, NIH [HHSN261200800001E]
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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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