miR-196a2基因多態(tài)性與兒童乙肝感染關聯(lián)分析
本文選題:mi + R-196a2; 參考:《重慶醫(yī)科大學》2017年碩士論文
【摘要】:目的:了解乙肝免疫預防效果,尤其是乙肝高危兒童的免疫預防效果,探討乙型肝炎病毒在母嬰垂直傳播中的影響因素,分析miR-196a2基因多態(tài)性與兒童乙肝感染的關聯(lián),為防控兒童乙肝發(fā)病及揭示相關發(fā)病機制提供科學依據(jù)。方法:收集2013年10月-2015年5月三家醫(yī)院(重慶醫(yī)科大學附屬第一醫(yī)院、附屬兒童醫(yī)院及成都市婦女兒童中心醫(yī)院)627名年齡6個月至12歲的漢族兒童作為研究對象。采取病例對照研究的流行病學方法,收集研究對象的基本資料、乙肝接種史、乙肝家族史等,收集兒童的靜脈血,采取ELISA法檢測乙肝血清學標志物,提取血樣DNA,篩選位于mi R-196a2基因上的SNP rs11614913,采取Sequenom MassArray方法對樣本進行基因分型。以HBsAg陽性的兒童為病例組(274名),以HBsAg陰性的兒童為對照組(353名),采用logistic回歸模型分析乙肝母嬰傳播的影響因素并分析miR-196a2 rs11614913與兒童乙肝感染的關系。結果:(1)親HBeAg陽性是乙肝高危兒童HBV母嬰傳播的重要危險因素(OR=10.270,95%CI:4.793-22.007)。(2)mi R-196a2基因多態(tài)性與兒童乙肝感染的關聯(lián)分析:miR-196a2CT的CT基因型與TT基因型相比在兩組中的分布有顯著差異,能減少兒童乙肝感染的風險(OR=0.60,95%CI:0.410-0.877),采用logistic回歸模型校正兒童性別、年齡及母親是否乙肝患者的因素后顯示,以TT基因型為對照,CT基因型能減少兒童乙肝感染風險(OR=0.638,95%CI:0.434-0.937)。構建基因模型:顯性模型分析發(fā)現(xiàn),rs11614913的TT基因型是兒童乙肝感染的保護因素(OR=0.637,95%CI:0.446-0.910)。超顯性模型分析發(fā)現(xiàn),rs11614913的CT基因型能降低兒童感染HBV的風險(OR=0.696,95%CI:0.506-0.957),共顯性模型分析發(fā)現(xiàn):rs11614913的CT基因型是兒童乙肝感染的保護因素(OR=0.600,95%CI:0.410-0.877),隱性模型分析無統(tǒng)計學差異。單因素分析結果顯示:在乙肝高危兒童HBV突破感染組和未感染組rs11614913的基因型及等位基因分布頻率差異無統(tǒng)計學意義。對乙肝高危兒童HBV突破感染的多種基因模型分析均未發(fā)現(xiàn)有統(tǒng)計學差異的結果。結論:(1)母親HBeAg陽性是乙肝母嬰傳播的危險因素。(2)位于mi R-196a2基因的SNP rs11614913與兒童HBV感染密切相關。(3)位于miR-196a2基因的SNP rs11614913與出生于HBsAg陽性母親的乙肝高危兒童HBV突破感染無關。
[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.
【學位授予單位】:重慶醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R725.1
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