Distribution of Four HIV Type 1-Resistance Polymorphisms (CCR5-Δ32, CCR5-m303, CCR2-64I, and SDF1-3′A) in the Bahraini Population

Abstract

Allelic differences of chemokine (C-C motif ) receptor 5 (CCR5) and CCR2, as well as the ligand for the chemokine receptor CXCR4, stromal-derived factor (SDF-1), are known to suppress HIV-1 transmission and to be involved in delay in HIV-1 disease progression. The aim of our study was to investigate the frequencies of four mutations that confer resistance to HIV-1: CCR5-Δ32, CCR5-m303, CCR2-64I, and SDF1-3′A among Bahrainis. We have studied the DNA polymorphisms in 304 unrelated healthy Bahraini individuals without any known history of HIV-1 infection or AIDS symptoms. The CCR5-Δ32 mutation was detected by PCR analysis, while the CCR5-m303, CCR2-64I, and SDF1-3′A mutations were detected by PCR-restriction fragment length polymorphism (PCR-RFLP) tests. Allele frequencies and the fit to the Hardy–Weinberg equilibrium were evaluated using the Arlequin population genetics application. The frequencies of the CCR5-Δ32, CCR2-64I, and SDF1-3′A alleles were 2.8%, 8.9%, and 26.5%, respectively. No mutant alleles were detected for the CCR5-m303 mutation in 304 individuals. We estimated the risk of AIDS onset (relative hazard), computed from the three-locus genotype data. This is the first report of these four mutations conferring resistance to HIV-1 in the Bahraini population. The presence of the CCR5-Δ32 allele among Bahrainis may be attributed to the admixture with people of European descent. The CCR2-64I allele and especially the SDF1-3′A allele are predominant in the Bahraini population and may be associated with resistance to fast HIV-1 infection in Bahrainis, and thus their genotyping can be used for prognosis in HIV-infected individuals.