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.
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
