Novel genetic associations and gene–gene interactions of chemokine receptor and chemokine genetic polymorphisms in HIV/AIDS

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Abstract
To investigate the influence of candidate polymorphisms on chemokine receptor/ligand genes on HIV infection and AIDS progression (HIV/AIDS). Fifteen polymorphisms of the CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCR6, CCL20, CCL22 and CXCL10 genes were analysed in 206 HIV-positive subjects classified as rapid progressors (RPs; n = 40), or non-RPs (NRPs; n = 166) and in 294 HIV-seronegative subjects. The polymorphisms were genotyped using minisequencing. Genetic models were tested using binomial logistic regression; non-parametric multifactor dimensionality reduction (MDR) was used to detect gene–gene interactions. The CCR3 rs3091250 [TT, adjusted odds ratio (AOR): 2.147, 95% confidence interval [CI] 1.076–4.287, P = 0.030], CCR8 rs2853699 (GC/CC, AOR: 1.577, 95% CI 1.049–2.371, P = 0.029), CXCL10 rs56061981 (CT/TT, AOR: 1.819, 95% CI 1.074–3.081, P = 0.026) and CCL22 rs4359426 (CA/AA, AOR: 1.887, 95% CI 1.021–3.487, P = 0.043) polymorphisms were associated with susceptibility to HIV infection. The CCL20 rs13034664 (CC, OR: 0.214, 95% CI 0.063–0.730, P = 0.014) and CCL22 rs4359426 (CA/AA, OR: 2.685, 95% CI 1.128–6.392, P = 0.026) variants were associated with rapid progression to AIDS. In MDR analyses revealed that the CXCL10 rs56061981 and CCL22 rs4359426 combination was the best model, with 57% accuracy (P < 0.001) for predicting susceptibility to HIV infection. Our results provide new insights into the influence of candidate chemokine receptor/ligand polymorphisms and significant evidence for gene–gene interactions on HIV/AIDS susceptibility.

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