miR-196a2基因多态性与儿童乙肝感染关联分析

发布时间：2018-04-15 07:11

本文选题：mi + R-196a2　；参考：《重庆医科大学》2017年硕士论文

【摘要】：目的:了解乙肝免疫预防效果,尤其是乙肝高危儿童的免疫预防效果,探讨乙型肝炎病毒在母婴垂直传播中的影响因素,分析miR-196a2基因多态性与儿童乙肝感染的关联,为防控儿童乙肝发病及揭示相关发病机制提供科学依据。方法:收集2013年10月-2015年5月三家医院(重庆医科大学附属第一医院、附属儿童医院及成都市妇女儿童中心医院)627名年龄6个月至12岁的汉族儿童作为研究对象。采取病例对照研究的流行病学方法,收集研究对象的基本资料、乙肝接种史、乙肝家族史等,收集儿童的静脉血,采取ELISA法检测乙肝血清学标志物,提取血样DNA,筛选位于mi R-196a2基因上的SNP rs11614913,采取Sequenom MassArray方法对样本进行基因分型。以HBsAg阳性的儿童为病例组(274名),以HBsAg阴性的儿童为对照组(353名),采用logistic回归模型分析乙肝母婴传播的影响因素并分析miR-196a2 rs11614913与儿童乙肝感染的关系。结果:(1)亲HBeAg阳性是乙肝高危儿童HBV母婴传播的重要危险因素(OR=10.270,95%CI:4.793-22.007)。(2)mi R-196a2基因多态性与儿童乙肝感染的关联分析:miR-196a2CT的CT基因型与TT基因型相比在两组中的分布有显著差异,能减少儿童乙肝感染的风险(OR=0.60,95%CI:0.410-0.877),采用logistic回归模型校正儿童性别、年龄及母亲是否乙肝患者的因素后显示,以TT基因型为对照,CT基因型能减少儿童乙肝感染风险(OR=0.638,95%CI:0.434-0.937)。构建基因模型:显性模型分析发现,rs11614913的TT基因型是儿童乙肝感染的保护因素(OR=0.637,95%CI:0.446-0.910)。超显性模型分析发现,rs11614913的CT基因型能降低儿童感染HBV的风险(OR=0.696,95%CI:0.506-0.957),共显性模型分析发现:rs11614913的CT基因型是儿童乙肝感染的保护因素(OR=0.600,95%CI:0.410-0.877),隐性模型分析无统计学差异。单因素分析结果显示:在乙肝高危儿童HBV突破感染组和未感染组rs11614913的基因型及等位基因分布频率差异无统计学意义。对乙肝高危儿童HBV突破感染的多种基因模型分析均未发现有统计学差异的结果。结论:(1)母亲HBeAg阳性是乙肝母婴传播的危险因素。(2)位于mi R-196a2基因的SNP rs11614913与儿童HBV感染密切相关。(3)位于miR-196a2基因的SNP rs11614913与出生于HBsAg阳性母亲的乙肝高危儿童HBV突破感染无关。
[Abstract]:Objective: to investigate the effect of hepatitis B immune prevention, especially in children with high risk of hepatitis B, to explore the influencing factors of hepatitis B virus in vertical transmission from mother to child, and to analyze the association between the polymorphism of miR-196a2 gene and the infection of hepatitis B in children.To provide scientific basis for prevention and control of children hepatitis B and revealing related pathogenesis.Methods: from October 2013 to May 2015, 627 Han nationality children aged 6 months to 12 years were selected from three hospitals (the first affiliated Hospital of Chongqing Medical University, affiliated Children's Hospital and Chengdu Women and Children Center Hospital).The basic data of the subjects, the history of hepatitis B vaccination and the family history of hepatitis B were collected by the epidemiological method of case-control study. The venous blood of children was collected, and the serological markers of hepatitis B were detected by ELISA method.The SNP rs11614913 located on the mi R-196a2 gene was selected and genotyped by Sequenom MassArray method.274 children with HBsAg positive and 353 controls with HBsAg negative were used to analyze the influencing factors of mother-to-child transmission of hepatitis B by logistic regression model and the relationship between miR-196a2 rs11614913 and hepatitis B infection in children.Results the positive HBeAg was an important risk factor for mother-to-child transmission of HBV in children with high risk of hepatitis B. The distribution of CT genotypes and TT genotypes were significantly different between the two groups.The risk of hepatitis B infection in children was reduced by using logistic regression model to correct the factors of children's sex, age and whether the mother was a hepatitis B patient. Compared with TT genotype, CT genotype could reduce the risk of hepatitis B infection in children. The risk of hepatitis B infection in children could be reduced by 0.638% 95% CI: 0.434-0.937 7.Construction of gene model: dominant model analysis showed that TT genotype of rs11614913 was the protective factor of hepatitis B infection in children.The analysis of overdominance model showed that the CT genotype of rs11614913 could reduce the risk of HBV infection in children. The codominance model analysis showed that the CT genotype of 1% rs11614913 was the protective factor of hepatitis B infection in children. There was no significant difference in recessive model analysis.The results of univariate analysis showed that there was no significant difference in genotype and allele distribution of rs11614913 between HBV breakthrough infection group and uninfected group in high risk children with hepatitis B.No significant difference was found in the analysis of multiple gene models for HBV breakthrough infection in children with high risk of hepatitis B.ConclusionsThe HBeAg positive of mother is the risk factor of mother-to-child transmission of hepatitis B.) the SNP rs11614913 located in mi R-196a2 gene is closely related to HBV infection in children. The SNP rs11614913 located in miR-196a2 gene is not related to HBV breakthrough infection in high risk children born to HBsAg positive mother.
【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】：R725.1

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