甲基转移酶样蛋白3/14基因甲基化水平对汉族儿童乙肝疫苗应答水平的影响  

Effect of methylation level of methyltransferase-like protein 3/14 geneon the level of response to hepatitis B vaccine in children of Han nationality

作　　者：李嘉铃 黄燕玲 董柏青 陈钦艳[3] 胡莉萍[3] 王超 苏永健 李海 LI Jia-ling;HUANG Yan-ling;DONG Bo-qing;CHEN Qin-yan;HU Li-ping;WANG Chao;SU Yong-jian;LI Hai(Department of Epidemiology,School of Public Health and Management,School of Basic Medicine,Guangxi University of Chinese Medicine,Nanning 530200,China;Guangxi Key Laboratory of Translational Medicine for Treating High Incidence Infectious Diseases with Integration of Traditional and Western Medicine,Nanning 530200,China;Guangxi Key Laboratory of Viral Hepatitis Prevention and Control Research,Guangxi CenteRfoRDisease Prevention and Control,Nanning 530029,China;Department of Biochemistry,School of Basic Medicine,Guangxi University of Chinese Medicine,Nanning 530200,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,南宁市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,南宁市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,南宁市530029 [4]广西中医药大学基础医学院生物化学教研室,南宁市530200

出　　处：《广西医学》2022年第7期689-693,726,共6页Guangxi Medical Journal

基　　金：国家自然科学基金(81760604,81703283);广西自然科学基金(2021GXNSFAA220110,2017GXNSFBA198086);广西中医药大学研究生教育创新计划(YCSZ2020020,YCXJ2021030)。

摘　　要：目的探讨甲基转移酶样蛋白(METTL)3/14基因甲基化水平对汉族儿童乙肝疫苗低/无应答现象的影响。方法根据接种乙肝疫苗后的应答水平,将263名汉族儿童分为低/无应答组(乙肝疫苗低应答和无应答,HBsAb<100 mIU/mL)104例和高/正常应答组(乙肝疫苗正常应答和高应答,HBsAb≥100 mIU/mL)159例。检测两组儿童METTL3/14基因的甲基化水平,采用非条件Logistic回归模型分析METTL3/14基因的甲基化水平与汉族儿童接种乙肝疫苗后低/无应答现象的相关性。结果低/无应答组METTL3_3基因31位点和66位点的甲基化水平均高于高/正常应答组(均P<0.05);而两组的METTL3_1、METTL3_2和METTL14基因各CpG位点的甲基化水平比较,差异均无统计学意义(均P>0.05)。非条件Logistic回归分析结果显示,METTL3_1基因28位点,以及METTL3_3基因31、66、141位点的甲基化水平升高是汉族儿童发生乙肝疫苗低/无应答的危险因素,METTL3_2基因200位点的甲基化水平升高是汉族儿童乙肝疫苗低/无应答的保护因素(均P<0.05)。结论METTL3_1基因28位点和METTL3_3基因31、66、141位点的甲基化水平升高可能增加汉族儿童发生乙肝疫苗低/无应答的风险,而METTL3_2基因200位点的甲基化水平升高可能降低汉族儿童发生乙肝疫苗低/无应答的风险。Objective To explore the effect of methylation level of the methyltransferase-like protein(METTL)3/14 gene on the phenomenon of low/no response to hepatitis B vaccine in children of Han nationality.Methods According to the response level afteRhepatitis B vaccination,263 children of Han nationality were divided into low/no response group(104 cases lowly responsive oRunresponsive to hepatitis B vaccine,with HBsAb<100 mIU/mL)and high/normal response group(159 cases normally oRhighly responsive to hepatitis B vaccine,with HBsAb≥100 mIU/mL).The methylation level of METTL3/14 gene was detected in children of both groups.The unconditional Logistic regression model was employed to analyze the correlation between the methylation level of METTL3/14 gene and the phenomenon of low/no response afteRhepatitis B vaccination in children of Han nationality.Results The low/no response group yielded higheRmethylation levels at METTL3_3 gene loci 31 and 66 as compared with the high/normal response group(all P<0.05);whereas there were no statistically significant differences between the two groups in the methylation levels at various CpG loci of METTL3_1,METTL3_2,and METTL14 genes(all P>0.05).The results of unconditional Logistic regression analysis showed that increases in the methylation levels at METTL3_1 gene locus 28 and METTL3_3 gene loci 31,66 and 141 were risk factors foRdeveloping low/no response to hepatitis B vaccine in children of Han nationality,and an elevation in the methylation levels at METTL3_2 gene locus 200 was a protective factoRfoRlow/no response to hepatitis B vaccine in children of Han nationality(all P<0.05).Conclusion Increases in the methylation levels at METTL3_1 gene locus 28 and METTL3_3 gene loci 31,66 and 141 may lead to the increased risk foRdeveloping low/no response to hepatitis B vaccine in children of Han nationality,whereas an elevation in the methylation level at METTL3_2 gene locus 200 may reduce the risk foRdeveloping low/no response to hepatitis B vaccine in children of Han nationality.

关 键 词：乙肝疫苗 低/无免疫应答 甲基转移酶样蛋白3 甲基转移酶样蛋白14 DNA甲基化 儿童 

分 类 号：R181[医药卫生—流行病学] R575.1[医药卫生—公共卫生与预防医学]