Polymorphism in the CCR5 gene promoter and HIV-1 infection in North Indians

Abstract

The clinical course and outcome of human immunodeficiency virus-1 (HIV-1) infection are highly variable among individuals. CCR5 is the primary coreceptor that mediates entry of HIV-1 (R5) into permissive host cells. In this study, five SNPs (59029G/A, 59353T/C, 59356C/T, 59402A/G, and 59653C/T) in the promoter region and a deletion of 32 bp (?32) in the CCR5 gene were evaluated in 180 chronically HIV-1-infected North Indians. The study showed the following: (1) the protective CCR5 Δ 32 allele was absent; (2) the frequency of CCR559402A allele in the HIV-infected people (66.4%) was higher than in healthy subjects (57.1%, ρ = 0.027) and in the CDC stage C patients (76%) versus stages A and B patients together (60%; ρ = 0.002); (3) homozygous CCR559402 AA genotype was significantly increased in the seropositive subjects (46.1%) compared with healthy control subjects (30.2%; ρ = 0.008) and in the CDC stage C patients (59.2%) compared with stage A and B subjects (37.6%, v = 0.007); and (4) an increased frequency of homozygous ACCAC haplotype was present in the seropositive stage C patients (32.4%) versus 15.6% in patients in stages A plus B (ρ = 0.013). These observations suggest an association of CCR559402A with increased likelihood of acquisition of HIV-1 and development of AIDS in the Asian Indian population. Further studies are required to confirm these findings and understand the effect of CCR5 polymorphisms on the outcome of HIV-1 infection.