第一部分候選基因單核苷酸多態(tài)性及其交互作用與HBV慢性肝病發(fā)生發(fā)展的關(guān)聯(lián)性分析目的:本部分的研究目的:1.應(yīng)用3種遺傳模型分析干擾素及其受體系列基因（IFNA1、IFNA2、IFNA5、IFNL4、IFNLR1、IFNAR2）、氧化應(yīng)激系列基因（CYBA、NCF4、NOX4、SOD2、GCLM）的單核苷酸多態(tài)性（single nucleotide polymorphisms,SNPs）及l(fā)nc-RP11-150O12.3外顯子區(qū)的rs2275959位點(diǎn)和HBV慢性肝病發(fā)生發(fā)展的關(guān)聯(lián)。2.分析同一染色體上物理位置接近的SNPs構(gòu)成的單倍體型和HBV慢性肝病發(fā)生發(fā)展的關(guān)聯(lián)。3.應(yīng)用3種統(tǒng)計(jì)方法分析各個(gè)系列SNPs的交互作用和HBV慢性肝病發(fā)生發(fā)展的關(guān)聯(lián)。方法:1. 候選基因SNPs的選擇。Pubmed數(shù)據(jù)庫(kù)檢索功能SNPs或者區(qū)域,這些SNPs或者區(qū)域可能會(huì)影響和HBV感染有關(guān)基因的m RNA的轉(zhuǎn)錄、蛋白質(zhì)的表達(dá),繼而影響HBV慢性肝病的發(fā)生發(fā)展。然后通過UCSC數(shù)據(jù)庫(kù)和Ensemble數(shù)據(jù)庫(kù)檢索其具體物理位置和在中國(guó)北方漢族人群中的罕見等位基因頻率（MAF）,Hapmap數(shù)據(jù)庫(kù)查詢單倍體... 

【文章來源】：河北醫(yī)科大學(xué)河北省

【文章頁(yè)數(shù)】：218 頁(yè)

【學(xué)位級(jí)別】：博士

【部分圖文】：

在HBV慢性肝病組和陰性對(duì)照組人群中用Haploview軟件對(duì)SNPs進(jìn)行的單體型分析

63Confoundingfactorssuchasgender,age,drinkingandsmokingwerecontrolledintheoperation*P＜0.05HighriskLow-riskEmpty圖2rs10903035,rs7525481,rs11249006交互作用模式圖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回歸分析陰性對(duì)照組與HBV慢性肝病組中與HBV慢性肝病有關(guān)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圖3rs7525481與rs10903035的交互作用效果圖Fig.3Interactioneffectsdiagramofrs7525481andrs10903035.RelativeriskwithcontributionsfromdifferentexposurecategoriesmarkedUisthecommonreferencecategory4.2干擾素及其受體系列基因SNPs和HBV自然清除能力的關(guān)聯(lián)性分析4.2.1SNPs和HBV自然清除能力關(guān)聯(lián)性的單因素分析Table15顯示了干擾素及其受體系列的14個(gè)SNPs在自愈組和HBV相關(guān)肝病組的基因型頻率分布。單因素分析顯示IFNLR1-rs4649203與HBV自發(fā)清除有關(guān)：攜帶野生純合體AA基因型的個(gè)體清除HBV能力是攜帶AG基因型個(gè)體的1.425(1.148,1.768)倍，顯性模型下，攜帶AA基因型的個(gè)體清除HBV能力是攜帶AG+GG基因型個(gè)體的1.386(1.133,1.697)倍。表15在HBV自然清除組和HBV慢性肝病組中進(jìn)行的與HBV自發(fā)清除能力有關(guān)的危險(xiǎn)因素的單因素分析Table15UnivariableanalysisofpredictivefactorswithregardtoHBVclearancebetweenHLDandnaturalclearanceLociClearancesHLDPOR(95%CI)IFNA1-rs1332190AA2168591GA2247420.0900.833(0.674,1.029)

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