Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans

• DOI: 10.1126/science.1193032
• Publication Date: 2010-07-15T22:40:09Z
• Authors: Giulio Genovese; David J. Friedman; Michael D. Ross; Laurence Lecordier; Pierrick Uzureau; Barry I. Freedman; Donald W. Bowden; Carl D. Langefeld; Taras K. Oleksyk; Andrea L. Uscinsk...; Andrea J. Bernhardy; Pamela J. Hicks; George W. Nelson; Benoit Vanhollebeke; Cheryl A. Winkler; Jeffrey B. Kopp; Etienne Pays; Martin R. Pollak
• Keywords: Chronic -- ethnology -- etiology -- genetics; Myosin Heavy Chains -- genetics; Biochimie; Lipoproteins; Molecular Motor Proteins -- genetics; African Americans -- genetics; Linkage Disequilibrium; Focal Segmental -- ethnology -- genetics; Kidney Failure; Cohort Studies; Glomerulosclerosis; Genetic; Gene Frequency; Trypanosomiasis; African -- genetics -- parasitology; Innate; Humans; Hypertension -- complications; Genetic Predisposition to Disease; Polymorphism; Recombinant Proteins -- metabolism; Selection; Alleles; Genetic Association Studies; Sequence Deletion; Parasitologie; Trypanosoma brucei rhodesiense -- metabolism; Glomerulosclerosis, Focal Segmental; Molecular Motor Proteins; Immunity; Biologie moléculaire; Single Nucleotide; Apolipoproteins -- blood -- genetics -- metabolism; Apolipoprotein L1; Immunity, Innate; 3. Good health; Black or African American; HDL -- blood -- genetics -- metabolism; Apolipoproteins; Logistic Models; Haplotypes; Case-Control Studies; Africa; Hypertension; Kidney Failure, Chronic; Biologie cellulaire; Lipoproteins, HDL

Out of Africa

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.