發(fā)布時間：2018-12-18 07:26

【摘要】：目的 慢性乙型肝炎（Chronic hepatitis B, CHB）已成為一種世界性慢性肝臟疾病。CHB與病毒基因型、年齡、環(huán)境因素、宿主因素等因素有關，更認為與遺傳因素有密切關系。到現(xiàn)在，國內(nèi)外許多研究指出PNPLA3基因多態(tài)性與NAFLD、酒精性肝病、丙型肝炎等肝臟疾病都有密切關系，然而現(xiàn)在還沒有關于PNPL A3基因rs738409多態(tài)性與慢性乙型肝炎之間聯(lián)系的報道研究。鑒于上述原因，在青島中國漢族人群慢性乙型肝炎患者中我們研究PNPLA3基因rs738409多態(tài)性的分布情況，探索青島地區(qū)漢族人群中PNPLA3基因多態(tài)性與慢性乙型肝炎的相關性。 方法 本研究通過病史的采集及生化數(shù)據(jù)結(jié)果的整理，共收集標本349例，其中CHB患者185例和健康對照受試者164例。在CHB組及正常組中，外周血進行DNA提取，采用多聚酶鏈式反應（PCR）擴增目的基因片段序列及應用基因測序方法檢測PNPLA3基因rs738409多態(tài)性，通過測序結(jié)果確定其基因型和等位基因的分布。CHB組與對照組各基因型是否具有群體代表性通過Hardy-weinbeurg遺傳平衡定律分析，非條件Logistic回歸分析基因變異及CHB相關因素之間的聯(lián)系。數(shù)據(jù)分析應用統(tǒng)計學軟件SPSS17.0。 結(jié)果 rs738409GG、GC和CC3種基因型在CHB組和對照組中均被檢出：CHB組GG型占13.0%，GC型占37.8%，CC型占49.2%；對照組GG型占6.7%，GC型占30.5%，，CC型占62.8%，基因型分布差異有統(tǒng)計學意義（P0.05）。CHB組與對照組rs738409等位基因頻率差異有統(tǒng)計學意義（P0.05）。其中CHB組rs738409G等位基因占31.9%，高于正常對照組的21.9%；G等位基因患CHB的風險是C等位基因的1.67倍（OR=1.67,95%CI:1.18-2.34, P=0.003）。經(jīng)混雜因素校正后，Logistic回歸模型分析結(jié)果顯示與與CC純合子攜帶者相比，攜帶危險等位基因G的GG+AG基因型增加慢性乙型肝炎的發(fā)生風險，比值比為1.76，95％可信區(qū)間為1.13-2.35。進一步說明PNPLA3基因與慢性乙型肝炎的發(fā)生有關。 結(jié)論 這研究顯示在青島地區(qū)中國漢族人中rs738409G基因增加慢性乙型肝炎的風險性，其作用機制有待進一步研究。
[Abstract]:Objective chronic hepatitis B (Chronic hepatitis B, CHB) has become a worldwide chronic liver disease. CHB is related to virus genotype, age, environmental factors, host factors and so on, and it is considered to be closely related to genetic factors. Up to now, many studies at home and abroad have pointed out that PNPLA3 gene polymorphism is closely related to NAFLD, alcoholic liver disease, hepatitis C and other liver diseases. However, no study has been reported on the association between PNPL A 3 gene rs738409 polymorphism and chronic hepatitis B. In view of the above reasons, we studied the distribution of PNPLA3 gene rs738409 polymorphism in Qingdao Chinese Han population, and explored the correlation between PNPLA3 gene polymorphism and chronic hepatitis B in Qingdao Han population. Methods A total of 349 specimens were collected through the collection of history and biochemical data, including 185 CHB patients and 164 healthy control subjects. In CHB group and normal group, DNA was extracted from peripheral blood, polymerase chain reaction (PCR) was used to amplify the target gene fragment sequence, and PNPLA3 gene rs738409 polymorphism was detected by gene sequencing. The distribution of genotypes and alleles was determined by sequencing. Whether the genotypes of CHB group and control group had population representativeness was analyzed by Hardy-weinbeurg genetic balance law. The relationship between gene variation and CHB related factors by non-conditional Logistic regression analysis. Applied Statistics Software SPSS17.0. for data Analysis Results the genotypes of rs738409GG,GC and CC3 were detected in CHB group and control group. The percentage of GG genotype in CHB group was 13.0% and that of GC type was 37.8%. In control group, GG type accounted for 6.7%, GC type accounted for 30.5% and CC type accounted for 62.8%. There was significant difference in genotype distribution between). CHB group and control group (P0.05). The risk of CHB in CHB group was 1.67 times higher than that in C allele (OR=1.67,95%CI:1.18-2.34, P0. 003). After adjustment for confounding factors, Logistic regression model analysis showed that the GG AG genotype carrying risk allele G increased the risk of chronic hepatitis B compared with that of CC homozygote carriers. The ratio is 1.76% and 95% confidence interval is 1.13-2.35. It is further indicated that PNPLA3 gene is associated with the development of chronic hepatitis B. Conclusion this study suggests that rs738409G gene increases the risk of chronic hepatitis B in Chinese Han population in Qingdao area, and its mechanism needs further study.
【學位授予單位】：泰山醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R512.62

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本文編號：2385556