PNPLA3rs738409基因多态性与成人非酒精性脂肪性肝病肝纤维化的相关性分析  

Association between polymorphism of PNPLA3 rs738409 and severity of fibrosis in adult nonalcoholic fatty liver disease

作　　者：王倩怡[1] 欧晓娟[1] 贾继东[1] 赵新颜[1] 王萍[1] 王晓明[1] 王宇[1] 段维佳[1] 王民[1] WANG Qian-yi;OU Xiao-juan;JIA Ji-dong(Liver Research Center,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院肝病中心,北京100050

出　　处：《临床和实验医学杂志》2020年第14期1464-1467,共4页Journal of Clinical and Experimental Medicine

基　　金：北京市医院管理局消化内科学科协同发展中心消化专项重点项目(编号:XXZ0304);首都医科大学附属北京友谊医院科研启动基金(编号:yyqdkt2017-8)。

摘　　要：目的探讨PNPLA3 rs738409基因多态性与成人非酒精性脂肪性肝病(NAFLD)患者肝纤维化程度的相关性。方法回顾性收集2016年1月至2018年6月于首都医科大学附属北京友谊医院经肝活检诊断为非酒精性脂肪性肝病的成人患者42例,应用Taqman探针分型法测定患者PNPLA3 rs738409的单核苷酸多态性。同时收集患者的一般资料、血液学检查、生化检查、影像学及病理资料。分析PNPLA3 rs738409基因型与NAFLD进展期纤维化的关系。结果PNPLA3 rs738409三种基因型占比CC、CG、GG分别为10例(23.8%)、19例(45.2%)和13例(31.0%)。三种不同等位基因型NAFLD患者的年龄、性别构成比、体重指数、合并症、丙氨酸氨基转移酶、谷氨酸转肽酶、空腹血糖、总胆固醇、甘油三酯等比较,差异均无统计学意义(P>0.05)。GG型患者的血小板计数[(161.4±67.7)×10^9/L vs.(209.0±52.1)×10^9/L,P=0.046]、凝血酶原活动度[(84.9±11.6)%vs.(97.9±18.8)%,P=0.012]均显著低于CC型患者,而肝脏硬度测定值显著高于CC型(17.5±7.8 kPa vs.10.9±6.5 kPa,P=0.043)。组织学方面,GG型患者脂肪变性程度和肝纤维化程度均高于GC型和CC型(P=0.028、0.015)。二元Logistic回归分析显示,在控制性别、年龄、糖尿病后,PNPLA3 rs738409 GG型是进展期纤维化的危险因素(OR=12.83,95%CI:1.69~97.19,P=0.013)。结论PNPLA3 rs738409基因多态性与NAFLD患者肝纤维化程度相关,GG型是进展期纤维化的危险因素。Objective To analyze the effect of the patatin-like phospholipase domain-containing protein 3(PNPLA3)gene rs738409 polymorphism on the severity of liver fibrosis in adult patients with nonalcoholic fatty liver disease(NAFLD).Methods Forty-two patients with biopsy-proven NAFLD in Beijing Friendship Hospital,Capital Medical University were enrolled from January 2016 to June 2018.The PNPLA3 rs738409 polymorphism was determined by TaqMan assays.The clinical,biochemical,radiological and pathological characteristics were collected.The relationship between PNPLA3 rs738409 genotype and NAFLD progressive fibrosis was analyzed.Results The PNPLA3 rs738409 genotype CC,CG and GG were observed in 10(23.8%),19(45.2%)and 13(31.0%)patients,respectively.There were no significant differences in the age,gender,body mass index(BMI),comorbidities,levels of serum a ALT,GGT,fasting glucose,total cholesterol and triglycerides among three groups of different genotype(P>0.05).Carriers of the GG genotype had significantly lower platelets[(161.4±67.7)×10^9/L vs.(209.0±52.1)×10^9/L,P=0.046]and prothrombin time activity(PTA)[(84.9±11.6)%vs(97.9±18.8)%,P=0.012],significantly higher values of liver stiffness measurement(17.5±7.8 kPa vs.10.9±6.5 kPa,P=0.043)than carriers of the CC genotype.Histologically,carriers of the GG genotype had more severe steatosis and fibrosis(P=0.028 and 0.015,respectively).Adjusted for age,gender and type 2 diabetes,PNPLA3 rs738409 GG genotype was associated with presence of advanced fibrosis(OR=12.83;95%CI:1.69-97.19;P=0.013)by binary logistic regression.Conclusion Polymorphism rs738409 in PNPLA3 is associated with severity of fibrosis in NAFLD patients,GG genotype is a risk factor of advanced fibrosis.

关 键 词：非酒精性脂肪性肝病 PNPLA3基因 肝纤维化 单核苷酸 多态性 

分 类 号：R575.5[医药卫生—消化系统]