title: Genetic variations and heterosexual HIV-1 infection: analysis of clustered genes encoding CC-motif chemokine ligands.
abstract: Several CC-motif chemokine ligands (CCLs) can block HIV-1-binding sites on CC-motif chemokine receptor 5 (CCR5) and inhibit viral entry. We studied single-nucleotide polymorphisms (SNPs) in genes encoding three CCR5 ligands (CCL3 (MIP-1a), CCL4 (MIP-1b)and CCL5 (RANTES)) along with an adjacent gene encoding a CCR2ligand (CCL2 (MCP-1)) to identify candidate markers for HIV-1 infection and pathogenesis. Analyses of 567 HIV-1 serodiscordant Zambian couples revealed that rs5029410C (in CCL3 intron 2) was associated with lower viral load (VL) in seroconverters, adjusted for gender and age (regression β=-0.57 log(10), P=4x10(-6)). Inaddition, rs34171309A in CCL3 exon 3 was associated with increased risk of HIV-1 acquisition in exposed seronegatives(hazard ratio=1.52, P=0.006 when adjusted for VL of the initially seropositive partner and genital ulcer/inflammation). SNPrs34171309 encodes a conservative Glu-to-Asp substitution. Fiven eighboring SNPs in tight linkage disequilibrium with rs34171309all showed similar associations with HIV-1 acquisition. How these multiple CCL3 SNPs may alter the occurrence or course of HIV-1 infection remains to be determined [corrected].
authors: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA.
authors: L
authors: L
authors: Hu
authors: W
authors: W
authors: Song
authors: I
authors: I
authors: Brill
authors: J
authors: J
authors: Mulenga
authors: S
authors: S
authors: Allen
authors: E
authors: E
authors: Hunter
authors: S
authors: S
authors: Shrestha
authors: J
authors: J
authors: Tang
authors: R A
authors: RA
authors: Kaslow
mesh_terms: D000483:Alleles; D019742:Chemokines, CC / Q000235:genetics* / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D020010:Heterosexuality; D006801:Humans; D008024:Ligands; D008297:Male; D005810:Multigene Family
chemical_list: D019742:Chemokines, CC; D008024:Ligands