Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals.
Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals.
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DOI：
10.1097/qad.0b013e328330b489
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发表时间：
2009-11-27
期刊：
影响因子：
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通讯作者：
Bochud PY
中科院分区：
文献类型：
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作者：
Pine SO;McElrath MJ;Bochud PY
Toll-like receptors (TLR) are innate immune sensors that are integral to resisting chronic and opportunistic infections. Mounting evidence implicates TLR polymorphisms in susceptibilities to various infectious diseases, including HIV-1. We investigated the impact of TLR single-nucleotide polymorphisms (SNPs) on clinical outcome in a sero-incident cohort of HIV-1-infected volunteers. We analyzed TLR SNPs in 201 antiretroviral treatment-naïve HIV-1 infected subjects from a longitudinal sero-incident cohort with regular follow-up intervals (median follow-up 4.2 years, interquartile range 4.4). Subjects were stratified into two groups according to either disease progression, defined as peripheral blood CD4+ T-cell decline over time, or peak and setpoint viral load. Haplotype-tagging SNPs from TLR2, TLR3, TLR4, and TLR9 were detected by mass-array genotyping, and CD4+ T-cell counts and viral load measurements were determined prior to antiretroviral therapy initiation. The association of TLR haplotypes with viral load and rapid progression was assessed by multivariate regression models using age and sex as covariates. Two TLR4 SNPs in strong linkage disequilibrium (1063A/G [D299G] and 1363C/T [T399I]) were more frequent among subjects with high peak viral load compared to low/moderate peak viral load (OR=6.65, 95% CI 2.19–20.46, P<0.001; adjusted P=0.002 for 1063A/G). In addition, a TLR9 SNP previously associated with slow progression was found less frequently among subjects with high viral setpoint compared to low/moderate setpoint (OR=0.29, 95% CI 0.13–0.65, P=0.003, adjusted P=0.04). This study suggests a potentially new role for TLR4 polymorphisms in HIV-1 peak viral load and confirms a role for TLR9 polymorphisms in disease progression.
