丙型肝炎病毒（HCV）感染是慢性肝病的主要原因。慢性HCV感染也是肝纤维化、肝硬化和肝细胞癌（HCC）的重要原因。HCV具有通过改变宿主免疫应答来逃避免疫监视的能力。此外，免疫相关基因的变异可导致对HCV感染的不同易感性，并影响对肝纤维化、肝硬化和HCC的易感性。人类白细胞抗原G（HLA-G）基因编码一种已知在母胎界面和免疫特权组织中表达的免疫调节蛋白。HLA-G基因3'未翻译区（3'UTR）对mRNA稳定性很重要，该区域的变异已知会影响基因表达。研究主要集中在14个碱基插入/缺失多态性，表明HLA-G 3'UTR与病毒感染的易感性相关，但HLA-G 3'UTR中的其他多态性变异可能也会影响HCV感染，因为它们以单倍型的形式遗传。本研究评估了286名患有HCV感染的患者的HLA-G 3'UTR多态性，并进行了连锁不平衡检验和单倍型组装，同时在129名健康对照组中也进行了相同的评估。单倍型UTR-1、UTR-2和UTR-3在HCV阳性患者中出现频率最高，分别为0.276、0.255和0.121。HCV阳性患者与对照组在统计学上没有显著差异，即使将患者按疾病结果（HCC、肝硬化或肝纤维化）分组也是如此。尽管如此，结果中观察到一些趋势，因此我们不能排除与高HLA-G表达相关的变异可能参与了HCV感染的易感性。© 2023 John Wiley＆Sons Ltd.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Chronic HCV infection is also an important cause of hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV has the capacity to evade immune surveillance by altering the host immune response. Moreover, variations in immune-related genes can lead to differential susceptibility to HCV infection as well as interfere on the susceptibility to the development of hepatic fibrosis, cirrhosis and HCC. The human leucocyte antigen G (HLA-G) gene codes for an immunomodulatory protein known to be expressed in the maternal-foetal interface and in immune-privileged tissues. The HLA-G 3' untranslated region (3'UTR) is important for mRNA stability, and variants in this region are known to impact gene expression. Studies, mainly focusing in a 14 bp insertion/deletion polymorphism, have correlated HLA-G 3'UTR with susceptibility to viral infections, but other polymorphic variants in the HLA-G 3'UTR might also affect HCV infection as they are inherited as haplotypes. The present study evaluated HLA-G 3'UTR polymorphisms and performed linkage disequilibrium test and haplotype assembly in 286 HCV infected patients who have developed fibrosis, cirrhosis or HCC, as well as in 129 healthy control subjects. Haplotypes UTR-1, UTR-2 and UTR-3 were the most observed in HCV+ patients, in the frequencies of 0.276, 0.255 and 0.121, respectively. No statistically significant difference was observed between HCV+ and control subjects, even when patients were grouped according to outcome (HCC, cirrhosis or fibrosis). Despite that, some trends in the results were observed, and therefore, we cannot rule out the possibility that variants associated to high HLA-G expression can be involved in HCV infection susceptibility.© 2023 John Wiley & Sons Ltd.