PNPLA3基因rs738409多态性与非酒精性脂肪性肝病遗传易感性的关联分析

发布时间：2019-04-17 11:35

【摘要】：目的：非酒精性脂肪性肝病(nonalcoholic fatty liver disease，NAFLD)在世界范围内发病率呈日益升高趋势，目前在我国慢性肝病中已排在了第二位，，近年来遗传易感性与NAFLD发病的关系越来越受到关注，相关基因的研究对探讨其发病机制及制定治疗方案至关重要。目前国外已证实含patatin样磷脂酶域3(PNPLA3)基因变异与NAFLD遗传易感性相关，国内对PNPLA3基因多态性与NAFLD发病的相关性研究尚较少，基于不同种族和地域的差异，本研究针对中原地区汉族人群，研究PNPLA3基因型和等位基因频率分布，探讨非酒精性脂肪性肝病与PNPLA3基因rs738409多态性之间的关联性。方法：本研究采用病例-对照研究，应用聚合酶链反应（PCR）、基因测序方法，对经肝活检确诊的NAFLD患者85例和健康对照者102例进行PNPLA3基因多态性的基因型检测，并收集其一般特征、生化结果及肝脏硬度值和肝脏组织学结果。应用spss17.0进行统计学分析，运用Hardy-Weinbeurg(H-W)平衡定律检测两组各基因型群体代表性是否良好，采用x2检验、单因素方差分析和非条件Logistic回归对实验数据进行处理。结果： NAFLD组PNPLA3基因rs738409CC基因型频率为16.47%、 GC基因型频率为41.18%、 GG基因型频率为42.35%，对照组对应基因型频率分别为44.12%、41.18%、14.70%；NAFLD组G等位基因频率分布为62.94%，对照组为35.29%，两组比较差异有统计学意义(p0.05)。采用非条件Logistic回归分析结果显示，GG基因型与CC基因型相比发生NAFLD的相对风险(OR)为3.11(95%CI2.04-4.76)。PNPLA3基因rs738409GG基因型BMI、TG、ALT、AST、FINS、肝脏硬度值高于CC基因型，肝组织学纤维化水平GG基因型高于GC基因型、CC基因型，GC基因型高于CC基因型，差异有统计学意义(p0.05)，而肝脏脂肪变程度、炎症程度三种基因型之间比较差异无统计学意义。结论：结果表明，在中原地区汉族人群中，PNPLA3基因rs738409多态性对NAFLD有遗传易感性作用，是影响NAFLD个体发病的重要因素之一；PNPLA3基因rs738409G等位基因与NAFLD肝脏纤维化程度有关。
[Abstract]:Objective: the incidence of non-alcoholic fatty liver disease (nonalcoholic fatty liver disease,NAFLD) is increasing day by day in the world. In recent years, more and more attention has been paid to the relationship between genetic susceptibility and NAFLD. At present, it has been proved that the patatin-like phospholipase domain 3 (PNPLA3) gene variation is associated with the genetic susceptibility to NAFLD in foreign countries. There are few studies on the relationship between PNPLA3 gene polymorphism and NAFLD incidence in China, based on the differences of different races and regions. In this study, the frequency distribution of PNPLA3 genotype and allele was studied in the Han population of Zhongyuan area, and the association between rs738409 polymorphism of PNPLA3 gene and non-alcoholic fatty liver disease was investigated. Methods: a case-control study was conducted to detect the genotype of PNPLA3 gene polymorphism in 85 patients with NAFLD diagnosed by liver biopsy and 102 healthy controls by polymerase chain reaction (PCR),) gene sequencing. The general characteristics, biochemical results, liver hardness and liver histology were collected. Spss17.0 was used for statistical analysis and Hardy-Weinbeurg (HMW) equilibrium law was used to detect whether the two groups were well represented. X2 test, one-way variance analysis and non-conditional Logistic regression were used to process the experimental data. Results: the rs738409CC genotype frequency of PNPLA3 gene was 16.47% in NAFLD group, 41.18% in GC genotype, 42.35% in GG genotype, and 44.12%, 41.18%, 14.70% in control group, respectively. The frequency distribution of G allele was 62.94% in NAFLD group and 35.29% in control group. There was significant difference between the two groups (p0.05). Non-conditional Logistic regression analysis showed that the relative risk of NAFLD in GG genotype and CC genotype was 3.11 (95%CI2.04-4.76). BMI,TG,ALT,AST,FINS, in PNPLA3 gene rs738409GG genotype was found to be 3.11 (95%CI2.04-4.76). The liver hardness value was higher than that of CC genotype, GG genotype was higher than GC genotype, CC genotype and GC genotype were higher than CC genotype in liver histologic fibrosis (p0.05), but the degree of hepatic steatosis was significantly higher than that of GC genotype (p0.05). There was no significant difference in the degree of inflammation among the three genotypes. Conclusion: the results show that rs738409 polymorphism of PNPLA3 gene has a genetic susceptibility to NAFLD and is one of the important factors affecting the pathogenesis of NAFLD in Han population of Central Plains, and the rs738409G allele of PNPLA3 gene is associated with the degree of hepatic fibrosis in NAFLD.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R575.5

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