APOBEC3G基因多态性与HBV感染后疾病转归的关系

目的 研究中国汉族人群载脂蛋白B mRNA编辑酶催化多肽3G(APOBEC3G)基因多态性与慢性乙型肝炎和肝硬化的关系.方法 应用焦磷酸测序,检测202例HBV感染自然痊愈者(对照组)、217例慢性乙型肝炎患者和216例乙型肝炎肝硬化患者APOBEC3G基因rs8177832位点多态性,确定其基因型及等位基因分布.同时通过建立DNA池技术初步对APOBEC3G基因的另外4个标签单核苷酸多态性位点(tagSNP)rs17000736、rs17496046,rs9622924和rs2899313进行疾病相关性的初步筛选;HBV DNA检测采用实时定量PCR.结果 rs8177832在中国汉族人群中以A/A为主要存在形式,其基因型频率和等位基因频率在对照组、慢性乙型肝炎组和乙型肝炎肝硬化组中的分布差异无统计学意义.慢性乙型肝炎组中携带G等位基因的患者HBV DNA水平为6.25 log10拷贝/ml,携带A等位基因的患者为5.54 log10拷贝/ml,t=2.111,P=0.036.rs17000736和rs9622924两位点在中国汉族人群中分别只有G/G和C/C一种单一基因型存在,rs17496046和rs2899313两位点分别以G等位基因和A等位基因为主,这4个tagSNP(rs17000736、rs17496046、rs9622924和rs2899313)在对照组、慢性乙型肝炎组和乙型肝炎肝硬化组中等位基因频率差异均无统计学意义.结论 汉族人群APOBEC3G基因中rs8177832位点的多态性可能与HBV的复制有关,但这5个tagSNP可能与HBV感染后疾病的进展无关.

The associations between polymorphisms of APOBEC3G and different outcomes of persistent HBV infection

Objective To investigate the associations between polymorphisms of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and different outcomes of HBV infection in the Chinese Han population. Methods Six hundred thirty-five chronic hepatitis B patients were divided into 3 groups: 202, 217 and 216 patients were HBV cleared, chronic hepatitis B, and with liver cirrhosis, respectively. Five tagSNPs (rs8177832, rs17000736, rs 17496046, rs9622924 and rs2899313) were genotyped by pyrosequencing. HBV viral loads were determined by real-time PCR method. Chi square was used for statistics. Results The majority of rs8177832 allele was A/A and the frequencies of rs8177832 allele among these groups were not significantly different (P > 0.05). HBV viral loads were higher in chronic hepatitis B patients with G allele than in chronic hepatitis B patients with A allele (P < 0.05). The rs17000736 and rs9622924 alleles were found only in G/G and C/C genotypes. There were also no significant differences in the other four SNPs alleles (rs17000736, rs17496046, rs9622924 and rs2899313) in these groups (P > 0.05). Conclusions rs8177832, rs17000736, rs17496046, rs17000736 and rs2899313 of the APOBEC3G gene might not be associated with HBV persistent infection in patients in this study. However, the rs8177832 polymorphism may be involved in inhibiting HBV replication.