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目的:探讨微小RNA 22(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-对照方法,收集1 020例确诊的乙型肝炎病毒(HBV)阳性HCC患者(病例组)和1 046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-22 rs6502892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 relationship between the genetic variation of miR-22 promoter region and the susceptibility to hepatitis B virus (HBV) -related hepatocellular carcinoma in Chinese population. Methods: A total of 1,020 venous blood samples of patients with confirmed HCC (case group) and 1046 healthy controls (control group) were collected by case-control method. The genotypes of rs6502892 (C → T) and rs721576 (A → G) in miR-22 promoter region were detected by TaqMan allelic method. Logistic regression was used to analyze the genotypes of the miR-22 promoter region. Relationship between genotypes and the risk of HBV related liver cancer. Results: The genotype distribution of rs6502892 was significantly different between the case group and the control group (P = 0.018), while the rs721576 genotype distribution was not significantly different between the two groups (P> 0.05). Compared with rs6502892 wild type (CC), rs6502892 genotype (CT / TT) significantly increased the risk of HBV-related hepatocellular carcinoma (adjusted OR = 1.23, 95% CI = 1.02-1.47, P = 0.029). Further stratification analysis showed that the risk effect of rs6502892 genotype (CT / TT) was more obvious in the age group of 52 years old, female, smoker and drinkers (all P <0.05), while the rs721576 mutation genotype / GG) decreased the risk of HBV-related hepatocellular carcinoma in both male and non-smokers (both P <0.05). CONCLUSIONS: The miR-22 rs6502892 mutant genotype (CT / TT) increases the risk of HBV-related hepatocellular carcinoma in China, while the rs721576 mutation (AG / GG) reduces the risk of HBV-related hepatocellular carcinoma in both male and non-smokers. This conclusion needs to be further related studies and functional studies confirmed.