Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
DNA Cell Biol. 2011 Dec;30(12):1027-32. doi: 10.1089/dna.2011.1238. Epub 2011 May 25.
The 14-bp insertion/deletion (indel) polymorphism located in the 3' UTR of the human leukocyte antigen-G (HLA-G) gene plays a role in several autoimmune and chronic inflammatory diseases. HLA-G expression is associated with hepatocellular carcinoma (HCC) prognosis, especially in early stage, with high expression independently associated with shortened overall survival and increased tumor recurrence. In the present study, we carried out a case-control study in a Chinese population (318 cases and 599 controls) to estimate the susceptibility to HCC associated with the 14-bp indel polymorphism. Logistic regression analysis showed that the heterozygote and the homozygote 14-bp ins/ins confer a lower risk of HCC (adjusted OR = 0.75, 95% CI: 0.57-1.01, p = 0.061; OR = 0.54, 95% CI: 0.30-0.98, p = 0.031, respectively). Hepatitis B virus (HBV) stratification analysis showed that the associations were stronger in the HBV-positive population. Immunohistochemical analysis further showed that HLA-G expression in HCC tissues with 14-bp del/del genotype was more prominent than for heterozygous and 14-bp ins/ins genotype (p < 0.01). Taken together, our results suggested that the HLA-G 14-bp indel polymorphism may be a marker for genetic susceptibility to HCC in Chinese populations. Further studies from different populations with larger sample size are warranted to validate our findings.
位于人类白细胞抗原-G(HLA-G)基因 3'UTR 中的 14 个碱基插入/缺失(indel)多态性在几种自身免疫和慢性炎症性疾病中发挥作用。HLA-G 的表达与肝细胞癌(HCC)的预后相关,尤其是在早期,高表达与总生存期缩短和肿瘤复发增加独立相关。在本研究中,我们在中国人群中进行了病例对照研究(318 例病例和 599 例对照),以评估与 14-bp indel 多态性相关的 HCC 易感性。Logistic 回归分析显示,杂合子和纯合子 14-bp ins/ins 赋予 HCC 较低的风险(调整后的 OR=0.75,95%CI:0.57-1.01,p=0.061;OR=0.54,95%CI:0.30-0.98,p=0.031)。乙型肝炎病毒(HBV)分层分析表明,在 HBV 阳性人群中相关性更强。免疫组织化学分析进一步表明,HLA-G 在 HCC 组织中表达 14-bp del/del 基因型比杂合子和 14-bp ins/ins 基因型更明显(p<0.01)。总之,我们的结果表明,HLA-G 14-bp indel 多态性可能是中国人群 HCC 遗传易感性的标志物。需要来自不同人群的更大样本量的进一步研究来验证我们的发现。