【摘要】：目的： 非酒精性脂肪性肝病(nonalcoholic fatty liver disease，NAFLD)在世界范圍內發(fā)病率呈日益升高趨勢，目前在我國慢性肝病中已排在了第二位，，近年來遺傳易感性與NAFLD發(fā)病的關系越來越受到關注，相關基因的研究對探討其發(fā)病機制及制定治療方案至關重要。目前國外已證實含patatin樣磷脂酶域3(PNPLA3)基因變異與NAFLD遺傳易感性相關，國內對PNPLA3基因多態(tài)性與NAFLD發(fā)病的相關性研究尚較少，基于不同種族和地域的差異，本研究針對中原地區(qū)漢族人群，研究PNPLA3基因型和等位基因頻率分布，探討非酒精性脂肪性肝病與PNPLA3基因rs738409多態(tài)性之間的關聯(lián)性。 方法： 本研究采用病例-對照研究，應用聚合酶鏈反應（PCR）、基因測序方法，對經肝活檢確診的NAFLD患者85例和健康對照者102例進行PNPLA3基因多態(tài)性的基因型檢測，并收集其一般特征、生化結果及肝臟硬度值和肝臟組織學結果。應用spss17.0進行統(tǒng)計學分析，運用Hardy-Weinbeurg(H-W)平衡定律檢測兩組各基因型群體代表性是否良好，采用x2檢驗、單因素方差分析和非條件Logistic回歸對實驗數(shù)據(jù)進行處理。 結果： NAFLD組PNPLA3基因rs738409CC基因型頻率為16.47%、 GC基因型頻率為41.18%、 GG基因型頻率為42.35%，對照組對應基因型頻率分別為44.12%、41.18%、14.70%；NAFLD組G等位基因頻率分布為62.94%，對照組為35.29%，兩組比較差異有統(tǒng)計學意義(p0.05)。采用非條件Logistic回歸分析結果顯示，GG基因型與CC基因型相比發(fā)生NAFLD的相對風險(OR)為3.11(95%CI2.04-4.76)。PNPLA3基因rs738409GG基因型BMI、TG、ALT、AST、FINS、肝臟硬度值高于CC基因型，肝組織學纖維化水平GG基因型高于GC基因型、CC基因型，GC基因型高于CC基因型，差異有統(tǒng)計學意義(p0.05)，而肝臟脂肪變程度、炎癥程度三種基因型之間比較差異無統(tǒng)計學意義。 結論： 結果表明，在中原地區(qū)漢族人群中，PNPLA3基因rs738409多態(tài)性對NAFLD有遺傳易感性作用，是影響NAFLD個體發(fā)病的重要因素之一；PNPLA3基因rs738409G等位基因與NAFLD肝臟纖維化程度有關。
[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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R575.5

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