RESUMO
Studies have investigated CCR5 haplotypes (HHA, HHB, HHC, HHD, HHE, HHF*1, HHF*2, HHG*1, HHG*2), defined by seven 5'UTR single nucleotide polymorphisms (SNPs), CCR2-V64I and CCR5Δ32, in HIV-1 disease. CCR5 cis-regulatory regions were sequenced, CCR2-V64I and CCR5Δ32 genotyped, and compared in HIV-1-infected black South Africans: 71 HIV-1 controllers (23 elite controllers, 37 viraemic controllers (VCs), 11 high viral load long-term non-progressors) and 74 progressors. The HHE haplotype and 3'UTR +2919â¯Tâ¯>â¯G SNP heterozygosity were underrepresented in total controllers and VCs vs. progressors (pâ¯=â¯.004; pâ¯=â¯.007 and pâ¯=â¯.002, pbonferroniâ¯=â¯0.032; pâ¯=â¯.004, respectively). Possession of the +2919â¯Tâ¯>â¯G SNP (dominant mode) was associated with HIV-1 progression (controllers vs. progressors: pâ¯=â¯.001, pbonferroniâ¯=â¯0.016). The +2919â¯Tâ¯>â¯G SNP is in linkage disequilibrium (LD; r2â¯=â¯0.73) with two 5'UTR SNPs (-2459Gâ¯>â¯A and -2135â¯Tâ¯>â¯C; r2â¯=â¯1: 5'UTR-2SNP-hap). The 5'UTR-2SNP-hap was lower in total controllers and VCs vs. progressors (pâ¯=â¯.003, pbonferroniâ¯=â¯0.048; pâ¯=â¯.01, respectively). Results suggest -2459Gâ¯>â¯A, -2135â¯Tâ¯>â¯C, andâ¯+â¯2919â¯Tâ¯>â¯G as key CCR5 variants in HIV-1 control.