本文關(guān)鍵詞： 乙肝病毒 突變 基因多態(tài)性 可誘導(dǎo)共刺激因子 核心啟動(dòng)子區(qū)　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景:乙肝病毒感染在全球范圍內(nèi)都是一個(gè)嚴(yán)重的公眾健康問題,尤其是在中國漢族人群中。在我們過去的研究中已經(jīng)證實(shí),可誘導(dǎo)共刺激因子(ICOS)的基因多態(tài)性與慢性乙肝病毒感染有關(guān)。乙肝病毒感染結(jié)局同時(shí)受病毒學(xué)的、免疫學(xué)的和宿主基因的因素影響。同時(shí),過去的研究已經(jīng)證實(shí)乙肝病毒突變對(duì)乙肝病毒感染后的結(jié)局有影響。這個(gè)研究的目的在于,進(jìn)一步探索ICOS單核苷酸多態(tài)性在HBV不同亞型感染中的影響及其與病毒突變共同作用對(duì)HBV感染結(jié)局的影響。方法:我們一共招募了1636個(gè)中國漢族人參與研究,其中包括:47個(gè)無癥狀的乙肝病毒攜帶者、353個(gè)慢性乙型病毒性肝炎病人、327個(gè)乙肝相關(guān)的肝硬化病人、193個(gè)乙肝相關(guān)的肝癌病人、464個(gè)自限性清除者和252正常的對(duì)照者。我們通過Taq Man SNP基因分型檢測與分析工具檢測上述參與者的DNA樣本中的ICOS基因的4個(gè)位點(diǎn)(rs11883722、rs10932029、rs1559931和rs4675379)。我們用直接測序法確定HBV在核心啟動(dòng)子區(qū)(Enh II/BCP/PC)的突變。在校正年齡和性別因素的情況下,采用二元邏輯回歸分析單核苷酸多態(tài)性及HBV突變的共同作用。結(jié)果:我們發(fā)現(xiàn)在C型HBV感染中,ICOS的rs10932029位點(diǎn)TC基因型與降低乙肝相關(guān)的肝硬化風(fēng)險(xiǎn)有相關(guān)性(P=0.003,OR=0.261)。在C型HBV感染中,核心啟動(dòng)子區(qū)A1762T(P=0.000,OR=4.784)、G1764A(P=0.019,OR=4.035)、A1762T/G1764A雙突變(P=0.000,OR=9.133)對(duì)于增加肝硬化的風(fēng)險(xiǎn)有顯著影響。進(jìn)一步的研究表明,rs10932029位點(diǎn)TC基因型分別與A1762T(P=0.014,OR=0.144)或A1762T/G1764A雙突變(P=0.014,OR=0.123)同時(shí)作用僅僅在C型HBV感染中明顯降低肝硬化的風(fēng)險(xiǎn)。然而,rs10932029位點(diǎn)TC基因型與G1764A共同作用與肝硬化的發(fā)生無明顯的相關(guān)性。結(jié)論:在C型HBV感染中,rs10932029位點(diǎn)TC基因型可能是一個(gè)肝硬化的保護(hù)因素。Rs10932029位點(diǎn)TC基因型與A1762T單突變或者A1762T/G1764A雙突變的共同作用,均能降低肝硬化的風(fēng)險(xiǎn)。
[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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.62

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