Genetic variations and heterosexual HIV-1 infection: analysis of clustered genes encoding CC-motif chemokine ligands View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-10-06

AUTHORS

L Hu, W Song, I Brill, J Mulenga, S Allen, E Hunter, S Shrestha, J Tang, R A Kaslow

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-1α), CCL4 (MIP-1β) and CCL5 (RANTES)) along with an adjacent gene encoding a CCR2 ligand (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 3) was associated with lower viral load (VL) in seroconverters, adjusted for gender and age (regression β=−0.57 log10, P=4 × 10−6). In addition, 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). SNP rs34171309 encodes a conservative Glu-to-Asp substitution. Five neighboring SNPs in tight linkage disequilibrium with rs34171309 all 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. More... »

PAGES

202-205

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/gene.2011.70

DOI

http://dx.doi.org/10.1038/gene.2011.70

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1035771313

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21975429


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