候选基因单核苷酸多态性与HBV慢性肝病发生发展的关联性分析及其生物学功能研究

发布时间：2021-01-17 04:14

　　第一部分候选基因单核苷酸多态性及其交互作用与HBV慢性肝病发生发展的关联性分析目的:本部分的研究目的:1.应用3种遗传模型分析干扰素及其受体系列基因（IFNA1、IFNA2、IFNA5、IFNL4、IFNLR1、IFNAR2）、氧化应激系列基因（CYBA、NCF4、NOX4、SOD2、GCLM）的单核苷酸多态性（single nucleotide polymorphisms,SNPs）及lnc-RP11-150O12.3外显子区的rs2275959位点和HBV慢性肝病发生发展的关联。2.分析同一染色体上物理位置接近的SNPs构成的单倍体型和HBV慢性肝病发生发展的关联。3.应用3种统计方法分析各个系列SNPs的交互作用和HBV慢性肝病发生发展的关联。方法:1. 候选基因SNPs的选择。Pubmed数据库检索功能SNPs或者区域,这些SNPs或者区域可能会影响和HBV感染有关基因的m RNA的转录、蛋白质的表达,继而影响HBV慢性肝病的发生发展。然后通过UCSC数据库和Ensemble数据库检索其具体物理位置和在中国北方汉族人群中的罕见等位基因频率（MAF）,Hapmap数据库查询单倍体... 

【文章来源】：河北医科大学河北省

【文章页数】：218 页

【学位级别】：博士

【部分图文】：

在HBV慢性肝病组和阴性对照组人群中用Haploview软件对SNPs进行的单体型分析

63Confoundingfactorssuchasgender,age,drinkingandsmokingwerecontrolledintheoperation*P＜0.05HighriskLow-riskEmpty图2rs10903035,rs7525481,rs11249006交互作用模式图Fig.2EpistaticinteractionforHBVchronichepaticdiseasesinvolvingrs10903035,rs7525481,rs11249006.rs10903035(0,1,2)=rs10903035(AA,AG,GG);rs7525481(0,1,2)=rs7525481(CC,CT,TT);rs11249006(0,1,2)=rs11249006(GG,AG,AA).ThescoresofHLDgroup(leftblackbarinboxes)andcontrolgroup(rightblackbarinboxes)areshownforeachgenotypecombination.表13Logistic回归分析阴性对照组与HBV慢性肝病组中与HBV慢性肝病有关的基因-基因相乘交互作用Table13MultiplicativeinteractionanalysisofSNPswithHBVchronichepaticdiseasesbetweenNegativeControlindividualsandHLDgroupbylogisticregressionVariableBS.EWaldPOR(95%CI)age(≥45years)0.1700.0676.3760.012*1.185(1.039,1.352)sex(Male)0.4580.10120.6680.000*1.580(1.297,1.925)smoke(Yes)0.9140.11365.4970.000*2.495(2.000,3.114)rs46492030.2460.1025.8330.016*1.278(1.047,1.561)rs10513930.4140.1567.0560.008*1.513(1.115,2.054)

66图3rs7525481与rs10903035的交互作用效果图Fig.3Interactioneffectsdiagramofrs7525481andrs10903035.RelativeriskwithcontributionsfromdifferentexposurecategoriesmarkedUisthecommonreferencecategory4.2干扰素及其受体系列基因SNPs和HBV自然清除能力的关联性分析4.2.1SNPs和HBV自然清除能力关联性的单因素分析Table15显示了干扰素及其受体系列的14个SNPs在自愈组和HBV相关肝病组的基因型频率分布。单因素分析显示IFNLR1-rs4649203与HBV自发清除有关：携带野生纯合体AA基因型的个体清除HBV能力是携带AG基因型个体的1.425(1.148,1.768)倍，显性模型下，携带AA基因型的个体清除HBV能力是携带AG+GG基因型个体的1.386(1.133,1.697)倍。表15在HBV自然清除组和HBV慢性肝病组中进行的与HBV自发清除能力有关的危险因素的单因素分析Table15UnivariableanalysisofpredictivefactorswithregardtoHBVclearancebetweenHLDandnaturalclearanceLociClearancesHLDPOR(95%CI)IFNA1-rs1332190AA2168591GA2247420.0900.833(0.674,1.029)

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