miRNA-146a、miRNA-196a2和miRNA-499单核苷酸多态性与肝细胞癌遗传易感性的相关性研究  

Association of single nucleotide polymorphisms of miRNA-146a,miRNA-196a2 and miRNA-499 with genetic susceptibility in hepatocellular carcinoma

作　　者：张立洪 胥广才[1] 张国栋 张培建[1] 陶立德[1] Zhang Lihong;Xu Guangcai;Zhang Guodong;Zhang Peijian;Tao Lide(Department of General Surgery,Affiliated Hospital of Yangzhou University,Yangzhou 225012,China)

机构地区：[1]扬州大学附属医院普外科,江苏扬州225012

出　　处：《肿瘤研究与临床》2021年第2期93-98,共6页Cancer Research and Clinic

摘　　要：目的探讨miRNA-146a(miR-146a)、miRNA-196a2(miR-196a2)和miRNA-499(miR-499)单核苷酸多态性与肝细胞癌遗传易感性的关系。方法采用病例对照研究设计。选取扬州大学附属医院2015年4月至2019年3月收治的肝细胞癌患者175例(肝细胞癌组)及同时期门诊体检的302名健康体检者(对照组)。应用聚合酶链反应-限制性片段长度多态性法检测两组外周血中miR-146a、miR-196a2和miR-499基因分型的分布情况,采用logistic回归模型分析3个miRNA的基因型、肝炎病毒感染者基因型与肝细胞癌遗传易感性的关系,采用Spearman相关分析法研究miR-146a基因多态性与人口学因素及临床特征间的关系。结果肝细胞癌组miR-146a单核苷酸多态性位点CC、CG、GG基因型分别为52例(29.7%)、86例(49.1%)、37例(21.1%),对照组分别为137名(45.4%)、135名(44.7%)、30名(9.9%),两组间基因型分布差异有统计学意义(χ^(2)=17.23,P<0.05);两组间miR-196a2和miR-499各基因型分布差异均无统计学意义(χ^(2)=0.51,P=0.776;χ^(2)=0.05,P=0.976)。单因素logistic回归分析显示,miR-146a基因型共显性模型中,与CC基因型相比,CG基因型(OR=1.96,95%CI 1.13~3.41,P=0.017)和GG基因型(OR=3.30,95%CI 1.85~5.89,P<0.01)发生肝细胞癌的风险升高;在显性模型中,与CC基因型相比,CG+GG基因型发生肝细胞癌的风险升高(OR=1.97,95%CI 1.33~2.93,P=0.001);在隐性模型中,与CG+GG基因型相比,GG基因型发生肝细胞癌的风险升高(OR=2.43,95%CI 1.44~4.11,P=0.001)。单因素logistic回归分析显示,在miR-196a2和miR-499基因型共显性、显性及隐性模型中,各基因型间肝细胞癌发生风险差异均无统计学意义(均P>0.05)。在乙型肝炎病毒(HBV)阳性的肝细胞癌患者中,miR-146a的CG和GG基因型发生肝细胞癌的风险分别是CC基因型的2.02倍(95%CI 1.06~5.07)和3.12倍(95%CI 1.66~10.07),CG+GG基因型是CC基因型的1.91倍(95%CI 1.85~3.38),GG基因型是CG+GG型的1.54倍(95%CI 1.15~6.08);在丙型肝�Objective To explore the association of miRNA-146a(miR-146a),miRNA-196a2(miR-196a2),and miRNA-499(miR-499)single nucleotide polymorphisms with genetic susceptibility in hepatocellular carcinoma.Methods A case-control study was designed.A total of 175 patients(hepatocellular carcinoma group)in Affiliated Hospital of Yangzhou University from April 2015 to March 2019 and 302 healthy people undergoing physical examination during the same period(the control group)were selected.The genotype distribution of miR-146a,miR-196a2 and miR-499 in the peripheral blood of the two groups were detected by using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Logistic regression model was used to analyze the association of 3 genotypes of miRNA,genotypes of hepatitis virus infectors with genetic susceptibility in hepatocellular carcinoma.The relationship between miR-146a gene polymorphism and demography factor as well as the clinical characteristics was also analyzed by using Spearman correlation analysis.Results In hepatocellular carcinoma group,miR-146a single nucleotide polymorphism of CC,CG,GG site genotypes had 52(29.7%)cases,86(49.1%)cases,37(21.1%)cases,respectively;in the control group,the corresponding genotypes had 137(45.4%)cases,135(44.7%)cases and 30(9.9%)cases,respectively,and the difference in genotype distribution of both groups was statistically significant(χ^(2)=17.23,P<0.05).There were no statistical differences in genotype distribution of miR-196a2 and miR-499(χ^(2)=0.51,P=0.776;χ^(2)=0.05,P=0.976).Single factor logistic regression analysis showed that in the co-dominant model of miR-146a genotype,genotypes of CG(OR=1.96,95%CI 1.13-3.41,P=0.017)and GG(OR=3.30,95%CI 1.85-5.89,P<0.01)had elevated risk of hepatocellular carcinoma compared with CC genotype.In the dominant model,the risk of hepatocellular carcinoma in CG+GG genotypes was increased compared with that in CC genotype(OR=1.97,95%CI 1.33-2.93,P=0.001);in the recessive model,the risk of hepatocellular carcinoma in GG genotyp

关 键 词：癌 肝细胞 微RNAS 多态性 单核苷酸 

分 类 号：R735.7[医药卫生—肿瘤]