Association of trypanolytic ApoL1 variants with kidney disease in African Americans
Submitted by Taras K Oleksyk on
PDF version| Title | Association of trypanolytic ApoL1 variants with kidney disease in African Americans |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Genovese, G, Friedman, DJ, Ross, MD, Lecordier, L, Uzureau, P, Freedman, BI, Bowden, DW, Langefeld, CD, Oleksyk, TK, Knob, ALUscinsk, Bernhardy, AJ, Hicks, PJ, Nelson, GW, Vanhollebeke, B, Winkler, CA, Kopp, JB, Pays, E, Pollak, MR |
| Journal | ScienceScience |
| Volume | 329 |
| Pagination | 841-5 |
| Date Published | Aug 13 |
| ISBN Number | 1095-9203 (Electronic)0036-8075 (Linking) |
| Accession Number | 20647424 |
| 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. |
