Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 16, 2018; 6(8): 167-175
Published online Aug 16, 2018. doi: 10.12998/wjcc.v6.i8.167
PNPLA3 rs738409 underlies treatment response in nonalcoholic fatty liver disease
Jin-Zhi Wang, Hai-Xia Cao, Jian-Neng Chen, Qin Pan
Jin-Zhi Wang, Hai-Xia Cao, Qin Pan, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Jian-Neng Chen, Department of Hepatology, Zhengxing Hospital, Zhangzhou 363000, Fujian Province, China
Author contributions: Wang JZ and Cao HX collected the data and contributed equally to this paper; Chen JN analyzed the data; Pan Q designed the study and wrote the paper.
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; and Program of the Committee of Science and Technology, No. 09140903500.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Qin Pan, MD, PhD, Professor, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Kongjiang Road NO. 1665, Yangpu District, Shanghai 200092, China. panqin@xinhuamed.com.cn
Telephone: +86-21-63846590 Fax: +86-21-25077340
Received: April 24, 2018
Peer-review started: April 24, 2018
First decision: May 11, 2018
Revised: May 16, 2018
Accepted: June 7, 2018
Article in press: June 8, 2018
Published online: August 16, 2018
Abstract

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 rs738409 related 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.

Keywords: Non-alcoholic fatty liver disease, Patatin-like phospholipase domain-containing protein 3, Treatment, Lifestyle, Pharmacotherapy, Surgery, Polymorphism

Core tip: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 imposes universal, yet distinctly different, impact on various therapies in nonalcoholic fatty liver disease (NAFLD) patients. As compared to those with C-allele, patients with PNPLA3 rs738409 G-allele (PNPLA3 148M variant) show grater improvement in response to lifestyle modification, dipeptidyl peptidase-4 inhibitor ingestion, and bariatric surgery. In contrast, NAFLD patients carrying PNPLA3 rs738409 C-allele (PNPLA3 148I variant) are much sensitive to both omega-3 poly-unsaturated fatty acids and statin intervention. These diversities in treatment response warrant a personalized, precise medicine in NAFLD by stratification of PNPLA3 rs738409 genotype.