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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2015; 21(34): 10054-10056
Published online Sep 14, 2015. doi: 10.3748/wjg.v21.i34.10054
PNPLA3 I148M variant affects non-alcoholic fatty liver disease in liver transplant recipients
Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Jun Cheng, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng
Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
Zheng-Tao Liu, Tian-Chi Chen, Xiao-Xiao Lu, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
Jun Cheng, Shu-Sen Zheng, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Zhou L and Zheng SS designed research; Liu ZT, Chen TC and Lu XX performed research; Xie HY, Zhou L and Zheng SS contributed reagents and analytic tools; Chen TC, Lu XX and Cheng J analyzed data; Liu ZT wrote the paper; and Xie HY, Zhou L and Zheng SS reviewed the paper.
Supported by National S and T Major Project, No. 2012ZX10002017; Foundation for Innovative Research Groups of the National Natural Science Foundation of China, Grant No. 81421062; and China Postdoctoral Science Foundation Project, No. 2015M570518.
Conflict-of-interest statement: Nothing to report.
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: Shu-Sen Zheng, Professor, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310003, Zhejiang Province, China. shusenzheng@zju.edu.cn
Telephone: +86-571-87236570 Fax: +86-571-87236570
Received: April 5, 2015
Peer-review started: April 7, 2015
First decision: May 18, 2015
Revised: June 3, 2015
Accepted: July 8, 2015
Article in press: July 8, 2015
Published online: September 14, 2015
Processing time: 162 Days and 11.9 Hours
Abstract

De novo non-alcoholic fatty liver disease (NAFLD) is a common late complication for long-term survivors after liver transplantation. Genomic studies confirmed that PNPLA3 I148M and TM6SF2 E167K polymorphisms affected NAFLD susceptibility in the general population. However, this association was not validated in survivors after liver transplantation (LT). We performed a cross-sectional survey to investigate this relationship. A comprehensive survey, including anthropometric measurements, fasting venous blood sampling, ultrasound, and questionnaires was performed in the short-term. The clinical indications and patient’s steatosis status before LT were collected from inpatient medical records. Sixty-five long-term recipients with a survival exceeding 10 years were enrolled in the final analysis. De novo NAFLD was more frequent in PNPLA3 GG carriers (0.33 vs 0.10 for GG vs CC + CG carriers, P = 0.018), while the genetic impact on NAFLD susceptibility was insignificant when categorized by the TM6SF2 polymorphism (0.19 in CC vs 0.14 in CT + TT carriers, P = 0.883). Multi-covariate analysis revealed that PNPLA3 exerted a significant genetic effect on de novo NAFLD following a recessive model (GG vs CC + CG, OR = 14.2, 95%CI: 1.78-113, P = 0.012). Compared to recipients with only the PNPLA3 GG allele or obesity (defined as body mass index > 25 kg/m2), steatosis was highly prevalent (71.4%) in PNPLA3 GG carriers with obesity. In conclusion, PNPLA3 I148M, but not TM6SF2 E167K, affects de novo NAFLD occurrence with a prominent interaction with obesity. Weight control might be a meaningful method to reduce the genetic susceptibility to NAFLD exerted by PNPLA3 variants.

Keywords: PNPLA3; TM6SF2; Non-alcoholic fatty liver disease; Liver transplantation; Recipient

Core tip: Previous genomic studies identified PNPLA3 I148M and TM6SF2 E167K polymorphisms as the most prominent genetic variations associated with non-alcoholic fatty liver disease (NAFLD) susceptibility in general populations. However, these impacts have never been evaluated in long-term liver transplant recipients. In a collection of survivors 10 years after liver transplantation, we found that the PNPLA3 I148M, but not TM6SF2 E167K polymorphism, affected de novo NAFLD predisposition and interacted with obesity. Our results revealed that liver transplant recipients might benefit from weight control to limit the deleterious effect exerted by genetic factors.