title: Novel genetic associations and gene-gene interactions of chemokine receptor and chemokine genetic polymorphisms in HIV/AIDS.
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 patients classified as rapid progressors (n = 40), or nonrapid progressors (n = 166), and in 294 HIV-seronegative patients.
  
  
  
  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.
  
  
  
  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 = 0.008) 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.
authors.affiliation: aDepartamento de Genética e Programa de Pós-graduação em Genética e Biologia Molecular da Universidade Federal do Rio Grande do Sul (PPGBM) bFundação Estadual de Produção e Pesquisa em Saúde (FEPPS) cServiço de Infectologia, Grupo Hospitalar Nossa Senhora da Conceição (GHC), Porto Alegre dUniversidade Luterana do Brasil (ULBRA), Canoas eInstituto de Ciências da Saúde, Universidade Feevale (FEEVALE), Novo Hamburgo, Rio Grande do Sul, Brazil.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Valverde-Villegas
authors.forename: Rúbia M
authors.initials: RM
authors.lastname: de Medeiros
authors.forename: Karine P
authors.initials: KP
authors.lastname: de Andrade
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Jacovas
authors.forename: Breno R
authors.initials: BR
authors.lastname: Dos Santos
authors.forename: Daniel
authors.initials: D
authors.lastname: Simon
authors.forename: Sabrina E
authors.initials: SE
authors.lastname: de Matos Almeida
authors.forename: José A B
authors.initials: JAB
authors.lastname: Chies
mesh_terms: D000328:Adult; D018925:Chemokines / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000235:genetics*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
chemical_list: D018925:Chemokines; D019707:Receptors, Chemokine