PNPLA3基因多态性与酒精性肝病遗传易感性的相关性研究

发布时间：2018-04-07 17:31

本文选题：酒精性性肝病　切入点：PNPLA3　出处：《山西医科大学》2014年硕士论文

【摘要】：目的酒精性肝病(alcoholicliverdisease,ALD）作为一种遗传-行为-环境相互作用导致的疾病,其发病机制非常复杂,包括酒精性脂肪肝、酒精性肝炎、酒精性肝硬化三种主要病理类型。近年来,国外许多研究指出PNPLA3（rs738409)基因多态性与ALD的脂肪代谢、肝脏炎症、肝纤维化密切相关,但是目前国内尚缺乏PNPLA3基因多态性与ALD的相关性的大样本病例对照研究,因此我们分析山西地区人群中ALD患者的PNPLA3（rs738409)基因多态性,并探讨PNPLA3基因多态性是否是ALD发病的高危因素。方法分别收集120例ALD患者和86例健康对照组的外周静脉抗凝血.应用聚合酶链反应(PCR)对目的片段进行扩增。通过基因测序方法明确PNPLA3（rs738409)基因类型。通过Hardy-weinbeurg遗传平衡定律分析两组的基因型是否具有群体代表性,通过非条件Logistic回归分析明确该基因变异与ALD发病之间的相关性。采用单因素方差分析明确该基因多态性与肝脏损伤指标及肝纤维化指标是否具有相关性。结果PNPLA3rs738409存在三种基因型，，分别为CC、CG、GG，各基因型在ALD组和健康对照组的频率分布有统计学意义(X2=7.195,P0.05)。非条件Logistic回归模型分析显示:GG基因携带者较CC基因携带者发生ALD的比值比(OR)为3.81(95%CI:3.03-4.79,P0.05)。且GG基因型的ALD患者肝纤维化指标明显高于GC、CC组（F=13.35.p0.001）。但各基因型的AST、ALT、GGT未见明显差异（F分别为0.3、1.667、1.682，P值均大于0.05）。结论:rs738409基因表型与ALD发病具有相关性，,是决定ALD个体遗传易感性的重要因素。且该基因多态性与肝纤维化风险相关。但未发现该基因多态性与肝细胞炎症具有相关性。
[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.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R575.5

【参考文献】