乙肝疫苗免疫应答反应与错义突变关联性

Correlation between immune response of hepatitis B vaccine and missense mutation

目的探讨乙肝疫苗免疫应答与个体错义突变间的关联性。方法本研究基于极端性状筛选遗传变异策略,对既往研究的49例"HBV强免疫应答"个体的全外显子组测序数据进行重新分析,从中筛选出与5个候选研究错义突变。本研究新纳入乙肝疫苗无(低)应答469例,乙肝疫苗高应答个体226例,对这5个候选突变行关联性分析,最后对关联阳性突变进行相关生物功能分析。结果两组TMEM176Ac.364A>G次要等位基因差异有统计学意义(P<0.05),变异c.364A>G可造成TMEM176A蛋白122氨基酸的理化性质发生较大改变,UniProtKB/Swiss-Prot数据库注释122位氨基酸正好位于TMEM176蛋白的跨膜区,而多物种蛋白质序列保守性分析也显示122位氨基酸处于个相当保守位置。结论TMEM176Ac.364A>G变异与个体接种乙肝疫苗后免疫应答反应存在关联性。通过相关生物信息学分析预测该变异可能对TMEM176A蛋白功能存在影响。

Objective To study the correlation between immune response of hepatitis B vaccine and missense mutation.Methods the study attempted the extreme phenotype comparison approach and renewable analysised the whole exome sequecing data of 49 individuals HBV strong immune response in previous studies.Five candidate missense mutations were screened out.In this study,469 individuals who had non(low)response to hepatitis B vaccine and 226 individuals who had high response to hepatitis B vaccine were newly enrolled.Finally,the related biological functions of the associated positive mutations were analyzed.Results Secondary allele differences in of TMEM176Ac.364A>G has statistically significant differences in two groups(P<0.05).Mutation c.364A>G can lead to the physicochemical property of 122 th amino acid residue has changed greatly.The 122 th amino acid locate on the transmembrane region of TMEM176A based on the annotation of UniProtKB/Swiss-Prot database;while conservative analysis of multi-species protein sequences also showed that 122 amino acids were in a relatively conservative position.Conclusion TMEM176 Ac.364 A>G was associated with response to HB vaccine;the mutation may influence the functional properties of protein TMEM176A by related bioinformatic analysis.