Publications & Reports

The role of SNPs in the alpha-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART.

Rajasuriar R, Booth DR, Gouillou M, Spelman T, James I, Solomon A, Chua K, Stewart G, Deeks S, Bangsberg DR, Muzoora C, Cameron PU, Hunt P, Martin J, Lewin SR
1] Department of Medicine, Monash University, Melbourne, Victoria, Australia [2] Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Abstract

We previously found an association between faster CD4+ T-cell recovery in HIV-infected patients receiving combination antiretroviral therapy (cART) and interleukin-7 receptor-alpha (IL-7Ralpha) haplotype-2 in a predominantly Caucasian cohort. This study aims to determine whether this association was also significant in Africans. Patients were recruited from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort (n=352). We used survival analysis and linear mixed modelling (LMM) to determine factors associated with CD4 T-cell recovery. Eight IL-7Ralpha single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n=57). Soluble (s)IL-7Ralpha levels were measured by ELISA. In UARTO, IL-7Ralpha haplotype-2 was associated with slower CD4 T-cell recovery following cART by using survival analysis (P=0.020) and no association was found with LMM (P=0.958). The tagging-SNP for IL-7Ralpha haplotype-2 (rs6897932) was associated with decreased sIL-7Ralpha (P<0.001). The haplotypes for the IL-7Ralpha were significantly different in Africans and Caucasians. Using IL-7Ralpha genotypes we found slower CD4 T-cell recovery in UARTO patients was still associated with rs6897932 (P=0.009) and rs3194051 was associated with faster CD4 T-cell recovery (P=0.006). Unlike Caucasians, we did not demonstrate a significant association between IL-7Ralpha haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7Ralpha SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts.Genes and Immunity advance online publication, 22 September 2011; doi:10.1038/gene.2011.65.

Publication

  • Journal: Genes and Immunity
  • Published: 01/01/2012
  • Volume: 13
  • Issue: 1
  • Pagination: 83-93

Author