IFNG基因DNA甲基化与乙型肝炎疫苗免疫应答水平的关联  

Association of DNA methylation of IFNG gene with no/low response to hepatitis B vaccine in children

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

出　　处：《中华预防医学杂志》2022年第7期926-931,共6页Chinese Journal of Preventive Medicine

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

摘　　要：目的分析广西汉族儿童IFNG基因DNA甲基化与乙型肝炎(乙肝)疫苗(HepB)免疫应答水平的关联性。方法采用非匹配病例对照方法,招募广西3家医院就诊的263名已完成HepB免疫程序的8~9月龄汉族儿童作为研究对象,将乙肝表面抗体浓度(抗-HBs)<100 mIU/ml设为病例组,≥100 mIU/ml设为对照组。采用多重PCR技术、重亚硫酸盐测序、使用Illumina平台对IFNG基因目标区域及其CpG位点进行DNA甲基化高通量测序。采用非条件logistic回归模型分析IFNG基因18个位点胞嘧啶-磷酸-鸟苷酸 DNA甲基化情况与HepB免疫应答水平的关联。结果病例组(104名)和对照组(159名)抗-HBs[M(Q1,Q3)]分别为62.34(30.06,98.88)mIU/ml和1 089.10(710.35,1 233.45)mIU/ml。病例组IFNG_(1)基因44和93位点甲基化水平差异高于对照组(P<0.05),非条件logistic回归模型显示,IFNG_(1)基因44位点(OR=1.18,95%CI:1.03~1.35)和93位点(OR=1.21,95%CI:1.07~1.38)DNA甲基化水平与HepB应答水平具有相关性。结论 IFNG_(1)基因44和93位点DNA甲基化水平改变可能是影响广西汉族儿童HepB应答水平的相关因素。Objective To explore the association of DNA methylation with immune response to hepatitis B(HepB)vaccine in Han nationality children from Guangxi province.Methods A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method.Children with the HepB surface antibody concentration(Anti-HBs)<100 mIU/ml was set as the case group and≥100 mIU/ml as the control group.Multiplex PCR and heavy sulfite sequencing were used to treat the samples.Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites.Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level.Results There were 104 children in the case group and 159 in the control group.The median(Q1,Q3)level of anti-HBs in two groups were 62.34(30.06,98.88)mIU/ml and 1089.10(710.35,1233.45)mIU/ml.The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group(P<0.05).The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44(OR=1.18,95%CI:1.03-1.35)and 93(OR=1.21,95%CI:1.07-1.38)locus was associated with the HepB response level.Conclusion The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

关 键 词：乙型肝炎疫苗 DNA甲基化 表观遗传学 免疫应答水平 

分 类 号：R725.1[医药卫生—儿科]