长链非编码RNA HULC遗传变异与中国南方人群原发性肝癌的关联研究  

Association analysis between long non-coding RNA HULC genetic variation and hepatocellular carcinoma in southern China

作　　者：魏志梅 林子博 邓煜盛 刘丽 郜艳晖 王辉 WEI Zhimei;LIN Zibo;DENG Yusheng;LIU Li;GAO Yanhui;WANG Hui(Department of Epidemiology and Health Statistics,School of Public Health,Guangdong Pharmaceutical University,Guangzhou 510310,China)

机构地区：[1]广东药科大学公共卫生学院,广东广州510310

出　　处：《广东药科大学学报》2018年第1期106-114,共9页Journal of Guangdong Pharmaceutical University

基　　金：广东省普通高校特色创新项目(2014KTSCX115);广东省自然科学基金(2014A030310039)

摘　　要：目的探究长链非编码RNA HULC(lncRNA HULC)遗传变异及其与环境交互作用对人群肝癌易感性关联的影响。方法采用病例对照研究及分层交互分析方法来分析HULC Single Nucleotide Polymorphisms(SNPs)(rs1328867A>G、rs2038540C>G、rs7763881A>C、rs7770772G>C、rs9379236G>C)与肝癌易感性的关联。结果 rs2038540的G变异基因型(GC+GG)携带者发生肝癌的风险是携带CC基因型者的1.278倍(OR=1.278,95%CI=1.013-1.612);携带rs7763881CC基因型者发生肝癌的风险是携带(AA+AC)基因型者的0.693倍(OR=0.693,95%CI=0.501-0.959);rs9379236 CC基因型携带者发生肝癌的风险是携带(GG+GC)基因型者的0.73倍(OR=0.73,95%CI=0.535-0.984)。分层分析显示,在年龄在大于60岁及以上者、有既往糖尿病病史者、吸烟者及重度吸烟者中,rs2038540的G变异基因型(GC+GG)增加了肝癌的发病风险;而在年龄为45~59岁者、男性、非吸烟饮酒者、重度吸烟者和没有既往糖尿病病史者中,rs7763881CC基因型降低了肝癌发病风险;在年龄为45~59岁者、男性、非吸烟者、没有既往糖尿病病史者中,rs9379236CC基因型是肝癌的保护因素。交互作用分析显示,rs2038540C>G位点变异与吸烟指数在增加肝癌发病风险上存在相乘交互效应。结论 LncRNA HULC的遗传变异与肝癌易感性有关,其中rs2038540的G变异基因型是肝癌的危险因素;而rs7763881A>C、rs9379236G>C基因型是肝癌的保护因素。Objective To study the effect of LncRNA HULC genetic variation and its interaction with the environment on the susceptibility to hepatocellular carcinoma(HCC).Methods A large case-control study and stratified interaction analysis were conducted to analyze the association of HULC Single Nucleotide Polymorphisms(SNPs)(rs1328867A>G,rs2038540C>G,rs7763881A>C,rs7770772G>C and rs9379236G>C)with susceptibility to HCC.Results The risk of HCC among the rs2038540patients with G-variant genotype(GC+GG)was1.278times higher than those with CC genotype(OR=1.278,95%CI=1.013-1.612).The risk of HCC among the patients with rs77383881CC genotype were0.693times lower than those with(AA+AC)genotype(OR=0.693,95%CI=0.501-0.959).The risk of HCC among the carriers with rs9379236CC genotype was0.73times lower than those with(GG+GC)genotype(OR=0.73,95%CI=0.535-0.984).Hierarchical analysis showed that rs2038540with G-variant genotype(GC+GG)increased the risk of HCC among those older than60years and those with the history of diabetes mellitus previously,smokers and heavy smokers.The rs7763881CC genotype,however,reduced the risk of developing HCC among those aged45to59years,men,non-smokers,heavy smokers and those with no history of diabetes previously.The rs9379236CC genotype also reduced the risk of developing HCC among individuals with45to59years of age,men,non-smokers and those without prior history of diabetes mellitus.Interaction analysis showed that there was a multiplication interaction effect between rs2038540C>G site mutation and smoking index which increased the risk of HCC.Conclusion The genetic variation of LncRNA HULC is related to the susceptibility to HCC.SNP rs2038540C>G with the genotype G mutation is a risk factor,however the rs7763881A>C and rs9379236G>C genotypes are protective factors.

关 键 词：长链非编码RNA HULC 单核甘酸多态性 肝细胞癌 关联研究 

分 类 号：R735.7[医药卫生—肿瘤]