Association of Toll-like receptor polymorphisms with HIV status in North Americans

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Single nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes TLR2-4 and TLR7-9, but not in TLR1 and TLR6, have been previously evaluated regarding HIV acquisition and disease progression in various populations, most of which were European. In the present study, we examined associations between a total of 41 SNPs in 8 TLR genes (TLR1-4, TLR6-9) and HIV status in North American subjects (total n = 276 [Caucasian, n = 102; African American, n = 150; other, n = 24]). Stratification of the data by self-identified race revealed that a total of 9 SNPs in TLR1, TLR4, TLR6, and TLR8 in Caucasians, and 2 other SNPs, one each in TLR4 and TLR8, in African Americans were significantly associated with HIV status at P < 0.05. Concordant with the odds ratios of these SNPs, significant differences were observed in the SNP allele frequencies between HIV+ and HIV− subjects. Finally, in Caucasians, certain haplotypes of single (TLR1, TLR4) and heterodimer (TLR2_TLR6) genes may be inferred as “susceptible” or “protective”. Our study provides in-depth insight into the associations between TLR variants, particularly TLR1 and TLR6, and HIV status in North Americans, and suggests that these associations may be race-specific.