Association of trypanolytic ApoL1 variants with kidney disease in African Americans

G Genovese, DJ Friedman, MD Ross, L Lecordier… - Science, 2010 - science.org
G Genovese, DJ Friedman, MD Ross, L Lecordier, P Uzureau, BI Freedman, DW Bowden…
Science, 2010science.org
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 …
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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