外周血miR-146基因多态性与乙型肝炎病毒感染患者肝硬化的易感性

Relationship between peripheral blood miRNA-146gene polymorphisms and susceptibility to liver cirrhosis in patients with hepatitis B virus infection

目的探讨外周血微小RNA(miR)-146基因多态性与乙型肝炎病毒感染患者肝硬化的易感性及其水平与病情严重程度的关系。方法选择杭州市西溪医院肝病科2018年5月-2020年6月收治的乙型肝炎肝硬化患者100例纳入研究组,选择同期医院收治的乙型肝炎非肝硬化患者60例作为对照组。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测两组miR-146a基因rs2910164位点基因型及表达水平,比较不同基因型患者乙型肝炎病毒载量、血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及总胆固醇(TC)水平。结果研究组miR-146a基因rs2910164位点CC基因型、C等位基因频率均高于对照组(P<0.05);100例慢性乙型肝炎肝硬化患者根据病情程度分为Child-pugh(A、B、C)三组,Child-pugh C组CC基因型频率高于Child-pugh A组及Child-pugh B组(χ^(2)=18.291、11.431,P均<0.001);miR-146a基因rs2910164位点CC基因型患者miR-146 mRNA、AST、ALT、TC水平高于TT/TC患者(P<0.05),HBV-DNA水平比较差异无统计学意义。结论miR-146a基因rs2910164位点多态性与HBV感染者发生肝硬化风险相关,miR-146mRNA水平对肝硬化程度判断具有一定的价值。

OBJECTIVE To explore the association between peripheral blood microRNA(miR)-146gene polymorphisms and susceptibility to liver cirrhosis in patients with hepatitis B virus(HBV)infection and severity of disease.METHODS A total of 100patients with hepatitis B liver cirrhosis who were treated in hepatopathy department of Hangzhou Xixi Hospital from May 2018to Jun 2020were assigned as the study group,meanwhile,60 hepatitis B without liver cirrhosis were set as the control group.The genotypes at rs2910164locus of miR-146a gene and the expression levels were detected by using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique;the levels of hepatitis B virus load,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total cholesterol(TC)were compared among the patients with different genotypes.RESULTS The frequencies of CC genotype at rs2910164locus of miR-146agene and allele C of the study group were significantly higher than those of the control group(P<0.05).The 100patients with chronic hepatitis B liver cirrhosis were divided into the Child-pugh A group,the Child-pugh B group and the Child-pugh C group according to the severity of disease.The frequency of CC genotype of the Child-pugh C group was significantly higher than that of the Child-pugh A group and the Child-pugh B group(χ^(2)=18.291,11.431,all P<0.001).The levels of miR-146mRNA,AST,ALT and TC of the patients with CC genotype at rs2910164locus of miR-146agene were significantly higher than those of the patients with TT/TC(P<0.05),there was no significant difference in the HBV-DNA level.CONCLUSIONThe polymorphism at rs2910164locus of miR-146agene is associated with the risk of liver cirrhosis in the patients with HBV infection,and the miR-146mRNA level has certain value in judgement of severity of liver cirrhosis.