title: 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.
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-α (IL-7Rα) 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-7Rα single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n=57). Soluble (s)IL-7Rα levels were measured by ELISA. In UARTO, IL-7Rα 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-7Rα haplotype-2 (rs6897932) was associated with decreased sIL-7Rα (P<0.001). The haplotypes for the IL-7Rα were significantly different in Africans and Caucasians. Using IL-7Rα 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-7Rα haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7Rα SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts.
authors.affiliation: Department of Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Rajasuriar
authors.forename: D R
authors.initials: DR
authors.lastname: Booth
authors.forename: M
authors.initials: M
authors.lastname: Gouillou
authors.forename: T
authors.initials: T
authors.lastname: Spelman
authors.forename: I
authors.initials: I
authors.lastname: James
authors.forename: A
authors.initials: A
authors.lastname: Solomon
authors.forename: K
authors.initials: K
authors.lastname: Chua
authors.forename: G
authors.initials: G
authors.lastname: Stewart
authors.forename: S
authors.initials: S
authors.lastname: Deeks
authors.forename: D R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: C
authors.initials: C
authors.lastname: Muzoora
authors.forename: P U
authors.initials: PU
authors.lastname: Cameron
authors.forename: P
authors.initials: P
authors.lastname: Hunt
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.forename: S R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D044383:Black People / Q000235:genetics; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D020395:Receptors, Interleukin-7 / Q000097:blood / Q000235:genetics*; D016019:Survival Analysis; D044465:White People / Q000235:genetics
chemical_list: D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain