The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART
Rajasuriar, R., Booth, D.R., Gouillou, M., Spelman, T., James, I., Solomon, A., Chua, K., Stewart, G., Deeks, S., Bangsberg, D.R., Muzoora, C., Cameron, P.U., Hunt, P., Martin, J. and Lewin, S.R. (2012) The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART. Genes and Immunity, 13 (1). pp. 83-93.
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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-7R alpha) 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-7R alpha single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n = 57). Soluble (s)IL-7R alpha levels were measured by ELISA. In UARTO, IL-7R alpha 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-7R alpha haplotype-2 (rs6897932) was associated with decreased sIL-7R alpha (P < 0.001). The haplotypes for the IL-7R alpha. were significantly different in Africans and Caucasians. Using IL-7R alpha 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-7R alpha haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7R alpha SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
|Publisher:||Nature Publishing Group|
|Copyright:||& 2012 Macmillan Publishers Limited|
|Notes:||This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License.|
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