HIV-associated nephropathy in African Americans

Abstract

Human immunodeficiency virus-1 (HIV-1) infection is associated with several glomerular syndromes, the most prevalent of which is HIV-associated focal segmental glomerulosclerosis (FSGS). At present, HIV-associated FSGS may account for up to 30% of patients in the United States entering end-stage renal disease (ESRD) as a consequence of FSGS. The mechanisms responsible for HIV-associated FSGS are not well defined, but evidence has been presented in favor of direct infection of renal parenchymal cells and toxicity of HIV-1 accessory proteins. HIV-associated FSGS has a striking predilection for patients of African descent. This likely has a genetic basis, although the gene or genes responsible have not yet been identified. One approach is to examine candidate genes for polymorphisms that are associated with disease. Another approach uses a genome-wide scan, relying upon linkage disequilibrium between DNA markers and the disease gene, to identify the causal gene or genes. African Americans are an admixed population, with genetic contributions from African, European, and Native American populations. In admixed populations, linkage disequilibrium between disease genes and marker genes can be exploited to identify disease genes, using an approach termed mapping by admixture linkage disequilibrium (MALD).