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APOL1 variations associated with kidney disease in African Americans

Posted Jul 19 2010 12:00am


Last week Martin Pollak and colleagues reported in Science that two independent variants in the nearby APOL1 (Apolipoprotein L-1) gene were responsible for the increased risk of renal disease disease and not the MHY9 gene. APOL1 is only ~20kb upstream of MYH9, however there is a strong recombination hot spot between the two genes, thus the entire effect of this locus on kidney disease in AA appears to be due to APOL1 based on strong statistical evidence.

AA with focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) were associated with two independent sequence variants in the APOL1 gene {FSGS odds ratio was 10.5 [95% confidence interval (CI) 6.0 to 18.4] and H-ESKD odds ratio was 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 is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. Trypanosoma can cause sleeping sickness and these variants can protect carriers from sleeping sickness.

The authors conclude/speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African-Americans. The mechanism of how APOl1, which is a soluble factor in human serum traveling with HDL particles, can predispose to kidney disease is unknown.
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