Strong Association of the rs4986790 Single Nucleotide Polymorphism (SNP) of the Toll-Like Receptor 4 (TLR4) Gene with Human Immunodeficiency Virus (HIV) Infection: A Meta-Analysis.

Human immunodeficiency virus (HIV) causes acquired immune deficiency syndrome (AIDS) and enters the host cell via CD4 and either CC-chemokine receptor 5 (CCR) or CXC-chemokine receptor 4 (CXCR4). HIV is directly recognized by toll-like receptor 4 (TLR4) and affects downstream immune-related signal pathways. In addition, stimulated TLR4 inhibits HIV-1 invasion, and the rs4986790 single nucleotide polymorphism (SNP) (D299G) of the TLR4 gene contributes to the risk of HIV-1 infection in an Indian population. To evaluate whether the rs4986790 SNP of the TLR4 gene is related to vulnerability to HIV-1 infection, we collected genetic information from HIV-1 patients in previous studies and performed an association analysis with a matched control population obtained from the 1000 Genomes Project. In addition, to strengthen the results of association analysis, we performed a meta-analysis. We identified a strong association between the rs4986791 SNP and susceptibility to HIV infection in HIV-infected patients in previous studies and a matched control population obtained from the 1000 Genomes Project. In addition, we found that the G allele of the rs4986791 SNP in the TLR4 gene is strongly related to susceptibility to HIV infection in three Caucasian populations (odd ratio = 2.29, 95% confidence interval: 1.72-3.07, p = 1.438 × 10-7) and all four populations (odd ratio = 2.22, 95% confidence interval: 1.74-2.84, p = 2 × 10-10) in a meta-analysis. To the best our knowledge, this was the first meta-analysis on the association between the rs4986791 SNP of the TLR4 gene and susceptibility to HIV infection.