Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy.
HLA. 2017 Mar;89(3):135-142. doi: 10.1111/tan.12959. Epub 2017 Jan 13.
Hepatitis C virus (HCV) is able to bypass the immune system modulating innate and adaptive immune response and blocking T helper 1 (Th1) cell production. Because the human leukocyte antigen (HLA)-G molecule has immunomodulatory properties inhibiting the function and production of natural killer and cytotoxic lymphocyte T cells, as well as promoting shift from Th1 toward Th2 response, we hypothesized its involvement in susceptibility to HCV infection.
Considering that HLA-G mRNA expression has been reported to be under genetic control, an association study was conducted analyzing 800 base pairs upstream the ATG at the 5'upstream regulator region (URR) and 850 base pairs from ATG to exon 3 and the 3'untranslated region (UTR) of HLA-G gene in Italian HCV-positive patients and uninfected controls.
Four 5'URR polymorphisms (-725C>G>T, -509C>G, -400G>A and -398G>A), 7 polymorphisms at coding region (+15G>A, +36G>A, +243G>A, insC506, 531G>C, delA615 and 685G>A), the +644G>T polymorphism, and 1 haplotype (TTGTTCCIGAC) showed different frequency distributions between HCV patients and uninfected controls.
The results from our study suggest a possible involvement of HLA-G in the risk modulation toward HCV infection.
丙型肝炎病毒 (HCV) 能够绕过免疫系统，调节先天和适应性免疫反应，并阻断 T 辅助 1 (Th1) 细胞的产生。由于人类白细胞抗原 (HLA)-G 分子具有免疫调节特性，可抑制自然杀伤细胞和细胞毒性 T 淋巴细胞的功能和产生，并促进 Th1 向 Th2 反应的转变，我们假设其参与了对 HCV 感染的易感性。
鉴于 HLA-G mRNA 表达受遗传控制，我们进行了一项关联研究，分析了意大利 HCV 阳性患者和未感染者中 HLA-G 基因 5'上游调控区 (URR) ATG 上游 800 个碱基对、ATG 到外显子 3 及 3'非翻译区 (UTR) 的 850 个碱基对。
发现 5'URR 有 4 个多态性 (-725C>G>T、-509C>G、-400G>A 和 -398G>A)、编码区有 7 个多态性 (+15G>A、+36G>A、+243G>A、insC506、531G>C、delA615 和 685G>A)、+644G>T 多态性和 1 个单倍型 (TTGTTCCIGAC) 在 HCV 患者和未感染者中的分布频率不同。
我们的研究结果表明 HLA-G 可能参与了 HCV 感染风险的调节。
