miR-22启动子区域的遗传变异与HBV相关肝癌发病风险的关系

Association of genetic variation in the promoter region of miR-22 gene and risk of HBV-related hepatocellular carcinoma

目的：探讨微小RNA22（miR-22）启动子区域的遗传变异与中国人群乙型肝炎病毒（HBV）相关肝癌易感性的关系。方法：采用病例一对照方法，收集1020例确诊的乙型肝炎病毒（HBV）阳性HCC患者（病例组）和1046例健康对照个体（对照组）静脉血标本。用TaqMan等位基因分型方法对miR-22启动子区域多态位点rs6502892（C→T）和rs721576（A→G）进行基因型检测，结合研究对象的基本资料，应用Logistic回归法分析不同基因型与HBV相关肝癌发病风险的关系。结果：rs6502892的基因型分布在病例组与对照组间差异有统计学意义（P=0．018），而rs721576的基因型的分布在两组间差异无统计学意义（P〉0．05）。与rs6502892野生型（CC）比较，rs6502892突变基因型（CT/TT）的HBV相关肝癌的发病风险明显增加（调整后OR=1．23，95％CI=1．02～1．47，P=0．029）。进一步的分层分析表明，rs6502892突变基因型（CT/TT）的危险效应在52岁以下年龄组、女性、吸烟者和饮酒者中更明显（均P〈0．05）；而rs721576突变基因型（AG/GG）在男性和非吸烟者中HBV相关肝癌的发病风险降低（均P〈0．05）。结论：miR-22rs6502892突变基因型（CT/TT）增加中国人群HBV相关肝癌的发病风险，而rs721576突变基因型（AG／GG）降低男性和非吸烟者患HBV相关肝癌的风险。这一结论有待进一步的关联研究以及功能学研究的证实。

Objective： To investigate the association of the genetic variation in the promoter region of microRNA 22 （miR- 22） and the susceptibility of hepatitis B virus （HBV）-related hepatocellular carcinoma （HCC） in Chinese population. Methods： Using a case-control approach, the venous blood samples from 1 020 HBV-positive HCC patients（case group） and 1 046 healthy subjects （control group） were collected. The genotypes of the polymorphic sites, rs6502892 （C→T） and rs721576 （A→G）, in the promoter region miR-22 gene were determined by TaqMan allelic discrimination assay. According to the general data of the enrolled subjects, the relationships between different genotypes and risk of HBV-related liver cancer were analyzed by Logistic regression. Results： The rs6502892 genotype distributions had statistical difference between case group and control group （P=0.018）, while the rs721576 genotype distributions showed no statistical difference （P〉0.05）. Compared with the rs6502892 wild-type （CC）, the variant rs6502892 genotypes （CT/TT） showed a significantly increased risk of HBV-related liver cancer （adjusted OR= 1.23, 95% CI= 1.02-1.47, P=0.029）. Further stratified analysis showed that the risk effect of variant rs6502892 genotypes （CT/TI＇） was more evident in those less than 52 years of age, and in females, smokers and alcoholics （all P〈O.05）, however, the variant rs721576 genotypes （AG/GG） showed decreased risk of HBV-related liver cancer in males and non-smokers （both P〈0.05）. Conclusion： In Chinese population, the variant rs6502892 genotypes （CT/Tr） ofmiR-122 gene are associated with an increased risk of HBVorelated liver cancer, whereas, the risk of HBV-related liver cancer is decreased in men and non-smokers with variant rs721576 genotypes. However, this conclusion still needs further confirmation with genetic association and functional studies.