MicroRNA基因单核苷酸多态性和DNA甲基化与儿童乙型肝炎疫苗无或低免疫应答的关联性  

Association of microRNA gene single nucleotide polymorphism and DNA methylation with no/low response to hepatitis B vaccine in children

作　　者：李嘉铃 董柏青 苏永健 吴琪俊 杨庆利 陈钦艳[3] 陈世艺 谭超 居昱[5] 李海 Li Jialing;Dong Baiqing;Su Yongjian;Wu Qijun;Yang Qingli;Chen Qinyan;Chen Shiyi;Tan Chao;Ju Yu;Li Hai(Department of Epidemiology,School of Public Health and Management,Guangxi University of Traditional Chinese Medicine,Nanning 530200,Guangxi,China;Guangxi Key Laboratory of Translational Medicine for Treating High-incidence Infectious Diseases with Integrative Medicine,Guangxi University of Traditional Chinese Medicine,Nanning 530200,Guangxi,China;Guangxi Key Laboratory for Control and Prevention of Viral Hepatitis,Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention,Nanning 530028,Guangxi,China;Department of Epidemiology and Health Statistics,School of Public Health,Guilin Medical College,Guilin 541000,Guangxi,China;Department of Emergent Infectious Disease Control and Prevention,Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention,Nanning 530028,Guangxi,China)

机构地区：[1]广西中医药大学公共卫生与管理学院流行病学教研室,广西南宁530200 [2]广西中医药大学广西高发传染病中西医结合转化医学重点实验室,广西南宁530200 [3]广西壮族自治区疾病预防控制中心广西病毒性肝炎防治研究重点实验室,广西南宁530028 [4]桂林医学院公共卫生学院流行病与卫生统计学教研室,广西桂林541000 [5]广西壮族自治区疾病预防控制中心急性传染病防制所,广西南宁530028

出　　处：《中国疫苗和免疫》2021年第4期370-376,共7页Chinese Journal of Vaccines and Immunization

基　　金：国家自然科学基金项目(81760604,81360443);广西自然科学基金项目(2013GXNSFBA019194);广西中医药大学研究生教育创新计划资助项目(YCSZ2020020,YCXJ2021030)。

摘　　要：目的探讨MicroRNA基因单核苷酸多态性(SNP)和DNA甲基化与儿童乙型肝炎疫苗(HepB)无或低免疫应答的关联性。方法选取广西壮族自治区三家医院出生且已完成3剂HepB接种的8-9月龄儿童,采集血标本,开展乙型肝炎病毒(HBV)DNA含量和血清标志物检测、MicroRNA基因位点的基因型/等位基因SNP检测和DNA甲基化检测;比较HepB无/低应答和正常/高应答儿童MicroRNA基因位点的基因型/等位基因分布和DNA甲基化β值(中位数)。结果miR196A2基因rs11614913位点的基因型(C/C、C/T、T/T)和等位基因(C、T)、miR499基因rs3746444位点的基因型(G/G、G/A、A/A)和等位基因(G、A)的分布在110名无/低应答和391名正常/高应答儿童之间均无显著性差异。miR196A22基因204位点、miR499B基因44、80、162位点的DNA甲基化β值在104名无/低应答和159名正常/高应答儿童之间均有显著性差异(0.028 vs 0.024,Z=-2.12,P=0.017;0.963 vs 0.956,Z=-2.43,P=0.007;0.965 vs 0.958,Z=-1.92,P=0.028;0.976 vs 0.973,Z=-1.93,P=0.027)。结论本研究中儿童HepB无/低免疫应答与MicroRNA基因SNP无显著性关联,而可能与miR196A22基因204位点、miR499B基因44、80和162位点的DNA甲基化存在关联。Objective To explore the association of single nucleotide polymorphism(SNP)and DNA methylation of microRNA genes with no/low immune response to hepatitis B vaccine(HepB)in children.Methods We enrolled 8-9-month-old children who were born in any of three hospitals of Guangxi Zhuang Autonomous Region and had received three doses of HepB.We collected blood samples to measure hepatitis B virus(HBV)DNA loads and test for presence of serum HBV markers,SNPs for genotypes/alleles of microRNA gene sites,and DNA methylation.We compared the genotype/allele distribution and DNA methylationβvalues(median)of microRNA sites between children with no/low and normal/high responses to HepB.Results There were no significant differences between 110 children with no/low response and 391 children with normal/high response in the distributions of genotypes(C/C,C/T,and T/T)and alleles(C and T)of the rs11614913 site of miR196 A2 genes,or for genotypes(G/G,G/A,and A/A)and alleles(G and A)of the rs3746444 site of miR499 genes.DNA methylationβvalues at the 204 site of miR196 A22 gene and the 44,80,and 162 sites of miR499 B gene were significantly different between 104 children with no/low response and 159 children with normal/high response(0.028 vs 0.024,Z=-2.12,P=0.017;0.963 vs 0.956,Z=-2.43,P=0.007;0.965 vs 0.958,Z=-1.92,P=0.028;0.976 vs 0.973,Z=-1.93,P=0.027).Conclusions No/low immune response to HepB in children was not significantly associated with SNPs of microRNA genes,but may be associated with DNA methylation at the 204 site of miR196 A22 and the 44,80,and 162 sites of miR499 B.

关 键 词：MicroRNA基因 单核苷酸多态性 DNA甲基化 乙型肝炎疫苗 免疫应答 

分 类 号：R181[医药卫生—流行病学]