Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2015; 21(3): 794-802
Published online Jan 21, 2015. doi: 10.3748/wjg.v21.i3.794
PNPLA3 I148M variant in nonalcoholic fatty liver disease: Demographic and ethnic characteristics and the role of the variant in nonalcoholic fatty liver fibrosis
Li-Zhen Chen, Yong-Ning Xin, Ning Geng, Man Jiang, Ding-Ding Zhang, Shi-Ying Xuan
Li-Zhen Chen, Yong-Ning Xin, Ning Geng, Man Jiang, Ding-Ding Zhang, Shi-Ying Xuan, Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China
Li-Zhen Chen, Ning Geng, Medical College of Qingdao University, Qingdao 266021, Shandong Province, China
Author contributions: Chen LZ drafted and wrote the manuscript; Xin YN, Geng N, Jiang M and Zhang DD revised the manuscript; and Xuan SY approved the final version.
Supported by National Natural Science Foundation of China No. 81170337/H0304.
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: Shi-Ying Xuan, PhD, Professor, Department of Gastroenterology, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao 266071, Shandong Province, China. dxyxyn@163.com
Telephone: +86-532-88905508 Fax: +86-532-88905293
Received: August 12, 2014
Peer-review started: August 13, 2014
First decision: September 15, 2014
Revised: September 25, 2014
Accepted: October 20, 2014
Article in press: October 21, 2014
Published online: January 21, 2015
Core Tip

Core tip: In this review, we summarize the association between the PNPLA3 I148M variant and nonalcoholic fatty liver disease (NAFLD), and especially its role in nonalcoholic fatty liver fibrosis. The variant is associated with NAFLD, but is predominant in women, not in men. The association may vary among different ethnic populations, but is not affected by the presence of metabolic syndrome. We speculate there is a pro-fibrogenic network that the PNPLA3 I148M variant may promote the development of fibrogenesis by activating the hedgehog signaling pathway, which, in turn, leads to the activation and proliferation of hepatic stellate cells, and excessive generation and deposition of extracellular matrix.