HIV nephropathy and the Duffy antigen/receptor for chemokines in African Americans

Background and Objectives: HIV nephropathy (HIVAN) is markedly racially bia sed in its distribution, occurring in about 10% of HIV infected African Ame ricans according to some studies. Based upon previous laboratory and epidem iological studies, the Duffy promoter polymorphism, which occurs almost exc lusively in individuals of African descent, has been postulated to be the p redisposing factor. We aimed to explore that relationship by directly genot yping individuals with HIV nephropathy to determine the proportion homozygo us for this mutation to test the hypothesis it was responsible for the gene tic component of this disease. We anticipated that if the pollymorphism was associated with HIV nephropathy all individuals would be homozygous for th is mutation. Method: Individuals with HIVAN proven on biopsy were identified from previo us studies and a pre-existing clinical database. This diagnosis was confirm ed by an experienced pathologist examining the biopsies in a blinded fashio n. PCR and RFLP strategies were used on the biopsy samples to genotype for the Duffy promoter polymorphism. The cases were compared to a control popul ation of HIV seronegative African Americans. Results: Twenty African American individuals with HIV nephropathy were succ essfully genotyped. Only nine were homozygous for the promoter mutation. Ni ne were heterozygous and two homozygous wild type. Furthermore, the frequen cy of the polymorphism did not differ from the background rate in the Afric an American population (OR = 0.788 95% confidence intervals 0.378-1.64). Conclusion: The Duffy promoter polymorphism was not disproportionately repr esented in persons with HIVAN calling into question any significant role in the pathogenesis of HIVAN.