PNPLA3 rs738409 underlies treatment response in nonalcoholic fatty liver disease  

作　　者：Jin-Zhi Wang Hai-Xia Cao Jian-Neng Chen Qin Pan 

机构地区：[1]Department of Gas- troenterology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine [2]Department of Hepatology,Zhengxing Hospital

出　　处：《World Journal of Clinical Cases》2018年第8期167-175,共9页世界临床病例杂志

基　　金：Supported by National Key Research and Development Plan"Precision Medicine Research",No.2017YFC0908903;National Natural Science Foundation of China,No.81070346,No.81270492,No.81470859,No.81270491 and No.81470840;State Key Development Program for Basic Research of China,No.2012CB517501;100 Talents Program,No.XBR2011007h;Program of the Committee of Science and Technology,No.09140903500

摘　　要：Non-alcoholic fatty liver disease(NAFLD)has now become the leading cause of chronic liver disease with its growing incidence worldwide.Patatin-like phospholipase domain-containing protein 3(PNPLA3)rs738409 C>G reflects one of the critical genetic factors that confers high-risk to NAFLD.However,the role of PNPLA3 polymorphism in NAFLD treatment remains uncertain.Here,the present review reveals that NAFLD patients with G-allele at PNPLA3 rs738409(PNPLA3 148M variant)are sensitive to therapies of lifestyle modification,dipeptidyl peptidase-4 inhibitors,and bariatric surgery.They exhibit much significant reduction of liver fat content,in concurrence with weigh loss and abolished insulin resistance,as compared to those of C-allele carriers.In contrast,patients bearing PNPLA3 rs738409 C-allele(PNPLA3 148I variant),instead of G-allele,demonstrate greater beneficial effects by omega-3 poly-unsaturated fatty acids and statin intervention.Improved adipose tissue-liver interaction and decrease in intrahepatic triglyceride efflux may contribute to the PNPLA3 rs738409related diversities in therapeutic efficacy.Therefore,PNPLA3 rs738409 underlies the response to a variety of treatments,which warrants a personalized,precise medicine in NAFLD on the basis of genotype stratification.Non-alcoholic fatty liver disease(NAFLD)has now become the leading cause of chronic liver disease with its growing incidence worldwide.Patatin-like phospholipase domain-containing protein 3(PNPLA3)rs738409 C>G reflects one of the critical genetic factors that confers high-risk to NAFLD.However,the role of PNPLA3 polymorphism in NAFLD treatment remains uncertain.Here,the present review reveals that NAFLD patients with G-allele at PNPLA3 rs738409(PNPLA3 148M variant)are sensitive to therapies of lifestyle modification,dipeptidyl peptidase-4 inhibitors,and bariatric surgery.They exhibit much significant reduction of liver fat content,in concurrence with weigh loss and abolished insulin resistance,as compared to those of C-allele carriers.In contrast,patients bearing PNPLA3 rs738409 C-allele(PNPLA3 148I variant),instead of G-allele,demonstrate greater beneficial effects by omega-3 poly-unsaturated fatty acids and statin intervention.Improved adipose tissue-liver interaction and decrease in intrahepatic triglyceride efflux may contribute to the PNPLA3 rs738409related diversities in therapeutic efficacy.Therefore,PNPLA3 rs738409 underlies the response to a variety of treatments,which warrants a personalized,precise medicine in NAFLD on the basis of genotype stratification.

关 键 词：Non-alcoholic FATTY liver disease Patatin-like PHOSPHOLIPASE domain-containing protein 3 Treatment LIFESTYLE PHARMACOTHERAPY Surgery Polymorphism 

分 类 号：R[医药卫生]