Leu72Metrs696217基因多态性与非酒精性脂肪性肝病遗传易感性的关系

Association of Leu72Met rs696217 gene polymorphism with genetic susceptibility to nonalcoholic fatty liver disease

目的探讨Leu72Met rs696217基因多态性与非酒精性脂肪性肝病(NAFLD)遗传易感性的关系。方法选择2019年7月至2021年8月中国科学院大学深圳医院收治的125例NAFLD患者作为研究对象(设为NAFLD组),另选择同期该院的104名健康体检者作为对照组。采用ELISA法测定受试者血清白蛋白(ALB)、ALT、AST、总胆红素(TBil)、总胆固醇(TC)、三酰甘油(TG)、凝血酶原时间(PT)和凝血酶原活动度(PTA)水平。应用ABI Prism 3730序列检测系统测定NAFLD组和对照组Leu72Met rs696217基因型,根据分型结果将NAFLD组分为GT+TT组(41例)和GG组(84例),并分析Leu72Met rs696217基因型与临床病理特征的关系。采用多因素logistic回归模型分析Leu72Met rs696217基因多态性与NAFLD遗传易感性的关系。结果与对照组比较,NAFLD组血清ALT、AST、TBil、PT、TC、TG水平均显著升高,而PTA、ALB水平均显著降低,差异均有统计学意义(P均<0.05)。NAFLD组Leu72Met rs696217 GG基因型频率高于对照组(67.20%比17.30%),Leu72Met rs696217 TT基因型频率低于对照组(16.0%比73.0%),差异均有统计学意义(P均<0.001)。NAFLD组Leu72Met rs696217 G等位基因频率高于对照组(75.6%比22.1%),Leu72Met rs696217 T等位基因频率低于对照组(24.4%比77.9%),差异均有统计学意义(P均<0.001)。与GT+TT组比较,GG组ALT、AST、TBil、PT、TC、TG水平显著升高,PTA、ALB水平显著降低,且脂肪变性程度、小叶内炎症反应程度、气球样变程度及纤维化程度均显著升高,差异均有统计学意义(P均<0.05)。多因素logistic回归模型分析结果显示,Leu72Met rs696217 GG基因型、Leu72Met rs696217 G等位基因均是NAFLD遗传易感性的独立危险因素(P均<0.05)。结论Leu72Met rs696217 GG基因型、Leu72Met rs696217 G等位基因与NAFLD遗传易感性具有一定相关性。

Objective This paper is to investigate the association between Leu72Met rs696217 gene polymorphism and the genetic predisposition of nonalcoholic fatty liver disease(NAFLD).Methods A total of 125 patients with NAFLD admitted to the Shenzhen Hospital of the University of Chinese Academy of Sciences between July 2019 and August 2021 were selected and assigned to the study group,and 104 healthy examinees in the same period were selected as the control group.The expression of serum Albumin(ALB),ALT,AST,total bilirubin(TBil),total cholesterol(TC),triglyceride(TG),prothrombin time(PT)and prothrombin activity(PTA)were detected by ELISA.The Leu72Met rs696217 polymorphism in the NAFLD group and the control group was determined by the ABI Prism 3730 sequence detection system.The NAFLD group was divided into the GT+TT group(n=41)and the GG group(n=84)according to the typing results.The relationship between Leu72Met rs696217 polymorphism and clinicopathological features was analyzed.The multivariate logistic regression model was used to analyze the association between Leu72Met rs696217 polymorphism and NAFLD genetic predisposition.Results Compared with the control group,the expression of ALT,AST,TBil,PT,TC,and TG in the NAFLD group are increased,while that of PTA and ALB are decreased,with statistically significant differences(P<0.05).The frequency of Leu72Met rs696217 GG genotype is higher in the NAFLD group than that in the control group(67.20%versus 17.30%),and the frequency of Leu72Met rs696217 TT genotype is lower in the NAFLD group than that in the control group(16.0%versus 73.0%),with statistically significant differences(P<0.001).The frequency of Leu72Met rs696217 G allele is higher in the NAFLD group than that in the control group(75.6%versus 22.1%),and the frequency of Leu72Met rs696217 T allele is lower in the NAFLD group than that in the control group(24.4%versus 77.9%),with statistically significant differences(P<0.001).Compared with the GT+TT group,the expression of ALT,AST,TBil,PT,TC,and TG in the GG group are increased,but that of PTA and ALB are decreased,while the degree of steatosis,inflammatory reaction,balloon-like change and fibrosis are increased,with statistically significant differences(P<0.05).The multivariate logistic regression analysis shows that Leu72Met rs696217 GG genotype and Leu72Met rs696217 G allele are independent risk factors for NAFLD genetic predisposition(P<0.05).Conclusion Leu72Met rs696217 GG genotype and Leu72Met rs696217 G allele are associated with NAFLD genetic predisposition.