T细胞活化信号分子基因miRNA结合区域SNP与乙肝疫苗弱应答的关联研究

Association between SNP of miRNA-binding sites of T cell activation-related genes and the non-response to hepatitis B vaccination

探讨与T细胞激活相关基因miRNA结合区域单核苷酸多态性(SNP)与乙肝疫苗弱应答的关联。采用病例对照设计,检测比较与T细胞激活相关基因miRNA结合区域SNP在乙肝疫苗正常应答组与弱应答组分布情况,及对乙肝疫苗抗体水平影响。经生物信息学预测,从T细胞激活相关的93个基因,发现30个相关基因miRNA结合区域有63个SNP,其中,有37个SNP位于11个基因的种子区,在中国人群最小等位基因频率(MAF)>10%的有20个。根据野生型等位基因和相应的突变型与miRNA结合自由能的改变情况≥2.80KJ/mol筛选出6个SNP作本研究备选SNP(rs1131579,rs17548629,rs12609318,rs344561,rs15927,rs3804033),rs12609318因为不符合HWE平衡而排除,比较77名弱应答者和207名正常应答者上述5个SNP基因型与等位基因型分布情况,差异无统计学意义(P>0.05),正常应答者的乙肝疫苗抗体滴度与单核苷酸多态性之间亦无关联(P>0.05)。本研究未能证明T细胞激活相关基因miRNA结合区域SNP与乙肝疫苗接种弱应答发生存在关联。

To investigate the association between polymorphisms in predicted target sites for micro-RNAs which related to T cell activation with non-response to hepatitis B vaccine.A case-control design,testing and comparing distribution of SNP in predicted target sites for micro-RNAs of T cell active genes of normal response group and non-response group to hepatitis B vaccine,and the impact of hepatitis B vaccine antibody levels.According to bioinformatic predictions,we found 63 SNP out of thirty T cell activation-related genes from 93 Tcell activation-related genes,of which there were 37 SNP located in the seed region of eleven genes,minimum allele frequency in the Chinese population（MAF）〉10% were 20.According to the wild-type allele and the corresponding mutant with miRNA binding free energy change of circumstances≧2.80KJ/mol,selected six candidate SNP（rs1131579,rs17548629,rs12609318,rs344561,rs15927,rs3804033）for this study,excluded rs12609318 for it did not meet HWE balance.We Selected 77non-responders and 207 normal responders.Between the two groups,the difference of distribution of alleles and allele frequency of blow 5SNP was not statistically significant（P〉0.05）,and there was no connection between single nucleotide polymorphisms with hepatitis B vaccine antibody titers of normal group（P〉0.05）.This research do not provide enough evidence to prove that polymorphisms in predicted target sites for micro-RNAs which related to T cell activation have a connection with poor immune response to hepatitis B vaccine.