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

• Published in: AIDS (London) Vol. 31; no. 9; pp. 1235 - 1243
• Main Authors: Valverde-Villegas, Jacqueline M, de Medeiros, Rúbia M, de Andrade, Karine P, Jacovas, Vanessa C, dos Santos, Breno R, Simon, Daniel, de Matos Almeida, Sabrina E, Chies, José A.B
• Format: Journal Article
• Language: English
• Published: England Copyright Wolters Kluwer Health, Inc 01.06.2017
• Subjects: Adult; AIDS/HIV; Chemokines - genetics; Disease Progression; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotyping Techniques; HIV Infections - genetics; Humans; Male; Middle Aged; Polymorphism, Genetic; Receptors, Chemokine - genetics; Retrospective Studies; Sequence Analysis, DNA
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0000000000001491

OBJECTIVE:To investigate the influence of candidate polymorphisms on chemokine receptor/ligand genes on HIV infection and AIDS progression (HIV/AIDS). DESIGN:Fifteen polymorphisms of the CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCR6, CCL20, CCL22 and CXCL10 genes were analysed in 206 HIV-positive patients classified as rapid progressors (n = 40), or nonrapid progressors (n = 166), and in 294 HIV-seronegative patients. METHODS:The polymorphisms were genotyped using minisequencing. Genetic models were tested using binomial logistic regression; nonparametric multifactor dimensionality reduction (MDR) was used to detect gene–gene interactions. RESULTS: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, AOR1.577, 95% CI 1.049–2.371, P = 0.029), CXCL10 rs56061981 (CT/TT, AOR1.819, 95% CI 1.074–3.081, P = 0.026) and CCL22 rs4359426 (CA/AA, AOR1.887, 95% CI 1.021–3.487, P = 0.043) polymorphisms were associated with susceptibility to HIV infection. The CCL20 rs13034664 (CC, OR0.214, 95% CI 0.063–0.730, P = 0.014) and CCL22 rs4359426 (CA/AA, OR2.685, 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 = 0.008) for predicting susceptibility to HIV infection. CONCLUSION: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.