YTHDF基因DNA甲基化与乙肝疫苗低/无免疫应答水平关系研究

Relationship between DNA methylation of YTHDF gene and low/no immune response level of hepatitis B vaccine

目的:从表观遗传角度探究N6-甲基腺苷(m 6 A)修饰相关的YTHDF基因DNA甲基化与乙肝疫苗接种者免疫低/无免疫应答水平的关系。方法:收集263例汉族儿童为研究对象。对儿童的外周血进行乙肝血清标志物检测,将乙型肝炎表面抗体(anti-HBs)浓度<100 mIU/ml者纳入病例组,将anti-HBs≥100 mIU/ml者纳入对照组。使用Methyl Target技术检测YTHDF基因位点的DNA甲基化水平,分析YTHDF基因81个位点CpG DNA甲基化水平与乙肝疫苗免疫应答水平的关系。结果:病例组纳入104例,对照组纳入159例,两组年龄和性别分布比较差异无统计学意义(均P>0.05)。病例组YTHDF1_1基因23位点、YTHDF1_2基因69位点与YTHDF1_2基因140位点甲基化水平均高于对照组(均P<0.05)。多因素非条件Logistic回归分析表明,YTHDF1_1基因23位点和YTHDF1_2基因140位点甲基化水平可能是乙肝疫苗低/无免疫应答的危险因素,而YTHDF1_2基因69位点和YTHDF2_1基因28位点甲基化水平可能是乙肝疫苗低/无免疫应答的保护因素(均P<0.05)。结论:YTHDF1_1基因23位点和YTHDF1_2基因140位点甲基化水平可能是乙肝疫苗低/无免疫应答的危险因素,YTHDF1_2基因69位点和YTHDF2_1基因28位点甲基化水平可能是乙肝疫苗低/无免疫应答的保护因素。

Objective:To explore the relationship between DNA methylation of YTHDF gene associated with N6-methyladenosine(m 6 A)modification and low/no immune response in hepatitis B vaccine recipients from the epigenetic point of view.Methods:A total of 263 Han nationality children were collected.Hepatitis B serum markers were detected in children’s peripheral blood.The children with hepatitis B surface antibody(anti-HBs)concentrations<100 mIU/ml were included in the case group and those with anti-HBs≥100 mIU/ml were included in the control group.Methyl Target was used to detect DNA methylation levels at the YTHDF gene locus and to analyze the relationship between CpG DNA methylation levels at 81 locus of the YTHDF gene and the level of immune response to hepatitis B vaccine.Results:There were 104 cases in the case group and 159 cases in the control group.There was no significant difference in age and sex distribution between the two groups(all P>0.05).The methylation levels at locus 23 of YTHDF1_1 gene,locus 69 of YTHDF1_2 gene and locus 140 of YTHDF1_2 gene in the case group were higher than those in the control group(all P<0.05).Multivariate unconditional Logistic regression analysis showed that methylation levels at locus 23 of YTHDF1_1 gene and locus 140 of YTHDF1_2 gene may be risk factors for low/no immune response to hepatitis B vaccine,and methylation levels at locus 69 of YTHDF1_2 gene and locus 28 of YTHDF2_1 gene may be protective factors for low/no immune response to hepatitis B vaccine(all P<0.05).Conclusion:Methylation levels at locus 23 of THDF1_1 gene and locus 140 of YTHDF1_2 gene may be risk factors for low/no immune response to hepatitis B vaccine,while the methylation levels at locus 69 of YTHDF1_2 gene and locus 28 of YTHDF2_1 gene may be protective factors for low/no immune response to hepatitis B vaccine.