APOL1 increases risk of renal failure but protects against sleeping sickness

Science 12 August, 2010:   An allele that increases the risk of hypertension induced renal failure 10 fold,  lyses Trypanosoma brucei rhodesiense and is more common in populations with exposure to sleeping sickness.

Summary from This Week in Science

Kidney disease is more common in African Americans than in Americans of European descent, and genetics is likely to be a major contributing factor. Genovese et al. (p. 841, published online 15 July) now show that African Americans who carry specific sequence variants in a gene on chromosome 22 encoding apolipoprotein L-1 (APOL1) have an increased risk of developing hypertension-attributed end-stage kidney disease or focal segmental glomerulosclerosis. These variants are absent from European chromosomes. Among the functions ascribed to APOL1 is the ability to lyse and kill trypanosomes. Intriguingly, APOL1 derived from the risk alleles, but not the “wild-type” allele, killed Trypanosoma brucei rhodesiense, which causes African sleeping sickness.

Science 13 August 2010:  Vol. 329. no. 5993, pp. 841 – 845    DOI: 10.1126/science.1193032

Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans

Giulio Genovese,^1,2,* David J. Friedman,^1,3,* Michael D. Ross,⁴ Laurence Lecordier,⁵ Pierrick Uzureau,⁵ Barry I. Freedman,⁶ Donald W. Bowden,^7,8 Carl D. Langefeld,^8,9 Taras K. Oleksyk,¹⁰ Andrea L. Uscinski Knob,⁴ Andrea J. Bernhardy,¹ Pamela J. Hicks,^7,8 George W. Nelson,¹¹ Benoit Vanhollebeke,⁵ Cheryl A. Winkler,¹² Jeffrey B. Kopp,¹¹ Etienne Pays,^5, Martin R. Pollak^1,13,

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.