Department of Medicine, Monash University, Melbourne, Victoria, Australia.
Genes Immun. 2012 Jan;13(1):83-93. doi: 10.1038/gene.2011.65. Epub 2011 Sep 22.
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.
我们之前在一个以白种人为主的队列中发现，接受联合抗逆转录病毒治疗 (cART) 的 HIV 感染者中，CD4+T 细胞恢复更快与白细胞介素-7 受体-α (IL-7Rα) 单倍型 2 相关。本研究旨在确定这一关联在非洲人中是否也有意义。从乌干达艾滋病农村治疗结局 (UARTO) 队列中招募了患者 (n=352)。我们使用生存分析和线性混合模型 (LMM) 来确定与 CD4 T 细胞恢复相关的因素。在非洲人和白种人中，我们共对 8 个 IL-7Rα 单核苷酸多态性 (SNP) 进行了基因分型 (n=57)。通过 ELISA 测量可溶性 (s)IL-7Rα 水平。在 UARTO 中，通过生存分析发现 IL-7Rα 单倍型 2 与 cART 后 CD4 T 细胞恢复较慢相关 (P=0.020)，而与 LMM 无关联 (P=0.958)。IL-7Rα 单倍型 2 的标记 SNP(rs6897932) 与 sIL-7Rα 降低相关 (P<0.001)。IL-7Rα 的单倍型在非洲人和白种人之间存在显著差异。使用 IL-7Rα 基因型，我们发现 UARTO 患者的 CD4 T 细胞恢复较慢仍与 rs6897932 相关 (P=0.009)，rs3194051 与 CD4 T 细胞恢复较快相关 (P=0.006)。与白种人不同，我们没有在非洲人中发现 IL-7Rα 单倍型 2 与 CD4 T 细胞恢复较快之间存在显著关联。cART 后与 CD4 T 细胞恢复相关的 IL-7Rα SNPs 在非洲和白种人队列中存在差异。
