Toll-like Receptor Polymorphism Associations With HIV-1 Outcomes Among Sub-Saharan Africans.

Mackelprang RD1, Bigham AW, Celum C, de Bruyn G, Beima-Sofie K, John-Stewart G, Ronald A, Mugo NR, Buckingham KJ, Bamshad MJ, Mullins JI, McElrath MJ, Lingappa JR.

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Abstract

Objective. We evaluated Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) for associations with HIV-1 acquisition, set-point and disease progression in African couples. Methods. Seven candidate and 116 haplotype-tagging SNPs (tagSNPs) were genotyped in 504 HIV-1 infected cases, and 343 seronegative controls. Results. TLR9 1635A/G was associated with reduced HIV-1 acquisition among HIV-seronegative controls with high but not low HIV-1 exposure (odds ratio [OR] = 0.7; P = .03 and OR = 0.9, P = .5, respectively). TLR7 rs179012 and TLR2 597C/T reduced set-point; the latter modified by time since HIV-1 acquisition. TLR8 1A/G reduced disease progression. Conclusions. TLR SNPs impact HIV-1 outcomes with epidemiologic factors modifying these relationships.

KEYWORDS:

Acute Infection, Genetics, HIV-1 acquisition, HIV-1 set-point, Heterosexual HIV-1 transmission, Progression, Risk Factors, Toll-like Receptors, Viral load