ICOS基因多态性和乙肝病毒突变共同作用对不同亚型HBV感染结局的影响

发布时间：2018-01-24 22:43

本文关键词： 乙肝病毒突变基因多态性可诱导共刺激因子核心启动子区　出处：《重庆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:乙肝病毒感染在全球范围内都是一个严重的公众健康问题,尤其是在中国汉族人群中。在我们过去的研究中已经证实,可诱导共刺激因子(ICOS)的基因多态性与慢性乙肝病毒感染有关。乙肝病毒感染结局同时受病毒学的、免疫学的和宿主基因的因素影响。同时,过去的研究已经证实乙肝病毒突变对乙肝病毒感染后的结局有影响。这个研究的目的在于,进一步探索ICOS单核苷酸多态性在HBV不同亚型感染中的影响及其与病毒突变共同作用对HBV感染结局的影响。方法:我们一共招募了1636个中国汉族人参与研究,其中包括:47个无症状的乙肝病毒携带者、353个慢性乙型病毒性肝炎病人、327个乙肝相关的肝硬化病人、193个乙肝相关的肝癌病人、464个自限性清除者和252正常的对照者。我们通过Taq Man SNP基因分型检测与分析工具检测上述参与者的DNA样本中的ICOS基因的4个位点(rs11883722、rs10932029、rs1559931和rs4675379)。我们用直接测序法确定HBV在核心启动子区(Enh II/BCP/PC)的突变。在校正年龄和性别因素的情况下,采用二元逻辑回归分析单核苷酸多态性及HBV突变的共同作用。结果:我们发现在C型HBV感染中,ICOS的rs10932029位点TC基因型与降低乙肝相关的肝硬化风险有相关性(P=0.003,OR=0.261)。在C型HBV感染中,核心启动子区A1762T(P=0.000,OR=4.784)、G1764A(P=0.019,OR=4.035)、A1762T/G1764A双突变(P=0.000,OR=9.133)对于增加肝硬化的风险有显著影响。进一步的研究表明,rs10932029位点TC基因型分别与A1762T(P=0.014,OR=0.144)或A1762T/G1764A双突变(P=0.014,OR=0.123)同时作用仅仅在C型HBV感染中明显降低肝硬化的风险。然而,rs10932029位点TC基因型与G1764A共同作用与肝硬化的发生无明显的相关性。结论:在C型HBV感染中,rs10932029位点TC基因型可能是一个肝硬化的保护因素。Rs10932029位点TC基因型与A1762T单突变或者A1762T/G1764A双突变的共同作用,均能降低肝硬化的风险。
[Abstract]:Background: hepatitis B virus infection is a serious public health problem worldwide, especially in Chinese Han population. The gene polymorphism of inducible costimulatory factor (ICOS) is associated with chronic hepatitis B virus infection. The outcome of hepatitis B virus infection is also affected by virology, immunology and host gene factors. At the same time. Previous studies have shown that HBV mutations have an impact on the outcome of HBV infection. To further explore the effect of ICOS single nucleotide polymorphisms in different subtypes of HBV infection and the effect of the interaction with virus mutation on the outcome of HBV infection. Methods:. We recruited a total of 1636 Chinese Han people to participate in the study. Among them, 47 asymptomatic hepatitis B carriers had 353 chronic hepatitis B patients and 327 hepatitis B related cirrhosis patients and 193 hepatitis B related liver cancer patients. 464 self-limited cleaners and 252 normal controls. We passed the Taq Man. SNP genotyping and analysis tools were used to detect the four loci of ICOS gene in the DNA samples of the participants (. Rs11883722. Rs10932029. Rs1559931 and rs4675379.We use direct sequencing method to determine HBV in the core promoter region Enh II / BCP / PC). When adjusting for age and sex factors. Single nucleotide polymorphisms (SNP) and HBV mutation were combined with binary logistic regression analysis. Results: we found that SNP was associated with type C HBV infection. There was a correlation between TC genotype of rs10932029 locus of ICOS and reducing the risk of hepatitis B related cirrhosis. The core promoter region A1762T ~ (0.000) ~ (0.000) ~ (4.784) ~ (G1764A) ~ (0.019) ~ (4.035)). A1762T / G1764A double mutation P 0.000 OR9.133) has a significant effect on increasing the risk of cirrhosis. The TC genotype of rs10932029 locus was 0.144 or A1762T / G1764A double mutation respectively (P = 0.014) or A1762T / G1764A (P = 0.014). OR0.123) combined treatment only significantly reduced the risk of cirrhosis in patients with type C HBV infection. There was no significant correlation between TC genotype and G1764A of rs10932029 locus and the occurrence of liver cirrhosis. Conclusion: in type C HBV infection, there is no significant correlation between TC genotype and G1764A. Rs10932029 locus TC genotype may be a protective factor for cirrhosis. Rs10932029 locus TC and A1762T single mutation or A1762T / G17. The interaction of 64A double mutation. Both can reduce the risk of cirrhosis.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62

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