發(fā)布時(shí)間：2018-04-07 17:31

  本文選題：酒精性性肝病　切入點(diǎn)：PNPLA3　出處：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的酒精性肝病(alcoholicliverdisease,ALD）作為一種遺傳-行為-環(huán)境相互作用導(dǎo)致的疾病,其發(fā)病機(jī)制非常復(fù)雜,包括酒精性脂肪肝、酒精性肝炎、酒精性肝硬化三種主要病理類型。近年來,國外許多研究指出PNPLA3（rs738409)基因多態(tài)性與ALD的脂肪代謝、肝臟炎癥、肝纖維化密切相關(guān),但是目前國內(nèi)尚缺乏PNPLA3基因多態(tài)性與ALD的相關(guān)性的大樣本病例對(duì)照研究,因此我們分析山西地區(qū)人群中ALD患者的PNPLA3（rs738409)基因多態(tài)性,并探討PNPLA3基因多態(tài)性是否是ALD發(fā)病的高危因素。 方法分別收集120例ALD患者和86例健康對(duì)照組的外周靜脈抗凝血.應(yīng)用聚合酶鏈反應(yīng)(PCR)對(duì)目的片段進(jìn)行擴(kuò)增。通過基因測(cè)序方法明確PNPLA3（rs738409)基因類型。通過Hardy-weinbeurg遺傳平衡定律分析兩組的基因型是否具有群體代表性,通過非條件Logistic回歸分析明確該基因變異與ALD發(fā)病之間的相關(guān)性。采用單因素方差分析明確該基因多態(tài)性與肝臟損傷指標(biāo)及肝纖維化指標(biāo)是否具有相關(guān)性。 結(jié)果PNPLA3rs738409存在三種基因型，，分別為CC、CG、GG，各基因型在ALD組和健康對(duì)照組的頻率分布有統(tǒng)計(jì)學(xué)意義(X2=7.195,P0.05)。非條件Logistic回歸模型分析顯示:GG基因攜帶者較CC基因攜帶者發(fā)生ALD的比值比(OR)為3.81(95%CI:3.03-4.79,P0.05)。且GG基因型的ALD患者肝纖維化指標(biāo)明顯高于GC、CC組（F=13.35.p0.001）。但各基因型的AST、ALT、GGT未見明顯差異（F分別為0.3、1.667、1.682，P值均大于0.05）。 結(jié)論:rs738409基因表型與ALD發(fā)病具有相關(guān)性，,是決定ALD個(gè)體遺傳易感性的重要因素。且該基因多態(tài)性與肝纖維化風(fēng)險(xiǎn)相關(guān)。但未發(fā)現(xiàn)該基因多態(tài)性與肝細(xì)胞炎癥具有相關(guān)性。
[Abstract]:Objective alcoholic liver disease (ALD) is a disease caused by heredity, behavior and environment interaction. The pathogenesis of ALD is very complicated, including alcoholic fatty liver, alcoholic hepatitis and alcoholic cirrhosis.In recent years, many foreign studies have pointed out that the polymorphism of PNPLA3 rs738409) gene is closely related to fat metabolism, liver inflammation and liver fibrosis of ALD. However, there is still a lack of large sample case-control studies on the association between PNPLA3 gene polymorphism and ALD in China.Therefore, we analyzed the polymorphism of PNPLA3 rs738409) gene in the population of Shanxi province, and discussed whether the polymorphism of PNPLA3 gene is the high risk factor of ALD.Methods Peripheral vein anticoagulant was collected from 120 patients with ALD and 86 healthy controls.The target fragment was amplified by polymerase chain reaction (PCR).The gene types of PNPLA3 rs738409 were identified by gene sequencing.The genetic equilibrium law of Hardy-weinbeurg was used to analyze whether the two groups had population representativeness, and the correlation between the variation of the gene and the pathogenesis of ALD was determined by non-conditional Logistic regression analysis.Univariate analysis of variance (ANOVA) was used to determine whether the gene polymorphism was associated with liver injury and hepatic fibrosis.Results there were three genotypes in PNPLA3rs738409, which were CCG GG. The frequency distribution of these genotypes in ALD group and healthy control group was statistically significant (P 0.05).Non-conditional Logistic regression model analysis showed that the ratio of ALD to ALD was 3.81% 95% CI: 3.03-4.79% (P 0.05) in 1% GG gene carriers compared with CC gene carriers.The hepatic fibrosis index in ALD patients with GG genotype was significantly higher than that in GCG-CC group (13.35.p0.001).However, no significant difference was found in the GGT of ASTGT of all genotypes (P > 0.05).Conclusion the phenotypes of the 1: rs738409 gene are associated with the pathogenesis of ALD, which is an important factor in determining the individual genetic susceptibility of ALD.The polymorphism of the gene was associated with the risk of liver fibrosis.However, no association between the gene polymorphism and hepatocyte inflammation was found.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R575.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 曹玉寧;李森林;;肝纖維化無創(chuàng)診斷的研究進(jìn)展[J];臨床肝膽病雜志;2011年02期

本文編號(hào)：1720159