Cis-regulatory genetic variants in the CCR5 gene and natural HIV-1 control in black South Africans.

ABSTRACT: 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 CCR5?32, in HIV-1 disease. CCR5 cis-regulatory regions were sequenced, CCR2-V64I and CCR5?32 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 +2919?T?>?G SNP heterozygosity were underrepresented in total controllers and VCs vs. progressors (p?=?.004; p?=?.007 and p?=?.002, pbonferroni?=?0.032; p?=?.004, respectively). Possession of the +2919?T?>?G SNP (dominant mode) was associated with HIV-1 progression (controllers vs. progressors: p?=?.001, pbonferroni?=?0.016). The +2919?T?>?G SNP is in linkage disequilibrium (LD; r2?=?0.73) with two 5'UTR SNPs (-2459G?>?A and -2135?T?>?C; r2?=?1: 5'UTR-2SNP-hap). The 5'UTR-2SNP-hap was lower in total controllers and VCs vs. progressors (p?=?.003, pbonferroni?=?0.048; p?=?.01, respectively). Results suggest -2459G?>?A, -2135?T?>?C, and?+?2919?T?>?G as key CCR5 variants in HIV-1 control.

SUBMITTER: Koor GW 

PROVIDER: S-EPMC6646080 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature