Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 26, 2018; 6(10): 355-364
Published online Sep 26, 2018. doi: 10.12998/wjcc.v6.i10.355
PNPLA3 rs139051 is associated with phospholipid metabolite profile and hepatic inflammation in nonalcoholic fatty liver disease
Ji-Jun Luo, Hai-Xia Cao, Rui-Xu Yang, Rui-Nan Zhang, Qin Pan
Ji-Jun Luo, Hai-Xia Cao, Rui-Xu Yang, Rui-Nan Zhang, Qin Pan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Author contributions: Pan Q conceived and designed the experiments; Luo JJ, Yang RX and Zhang RN performed the experiments; Luo JJ and Cao HX analyzed the data; Pan Q wrote the paper; Luo JJ and Cao HX contributed equally to this work.
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.
Institutional review board statement: The study was reviewed and approved by the Xinhua Hospital Ethics Committee Affiliated to Shanghai Jiaotong University School of Medicine.
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, 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: June 19, 2018
Peer-review started: June 19, 2018
First decision: July 11, 2018
Revised: July 16, 2018
Accepted: August 3, 2018
Article in press: August 4, 2018
Published online: September 26, 2018
Processing time: 100 Days and 4.3 Hours
ARTICLE HIGHLIGHTS
Research background

Genome-wide association analysis and clinical investigations have found that single nucleotide polymorphisms (SNPs) of patatin-like phospholipase domain containing 3 (PNPLA3) underlie the genetic susceptibility of nonalcoholic fatty liver disease (NAFLD), independent of gender, age and ethnic background.

Research motivation

The understanding of the SNP-specific impact on serum lipids and their correlation with pathological characteristics is still limited and controversial. In this study, the authors stratified Chinese Han patients with biopsy-proven NAFLD by genotyping their PNPLA3 SNPs.

Research objectives

In this study, the authors investigated the effect of PNPLA3 polymorphisms on serum lipidomics and pathological characteristics of NAFLD.

Research methods

Thirty-four biopsy-proven NAFLD patients from China were subjected to stratification by genotyping their SNPs in PNPLA3. Ultra-performance liquid chromatographytandem mass spectrometry was employed to characterize the effects of PNPLA3 SNPs on serum lipidomics. The variant-based scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was performed to uncover the actions of lipidomics-affecting PNPLA3 SNPs in NAFLD-specific pathological alternations.

Research results

PNPLA3 SNPs demonstrated extensive association with the serum lipidomics, especially phospholipid metabolites of NAFLD patients. The significant correlation of PNPLA3 rs139051 and inflammation grading further convinced its pathological role that was based on the modulation of phospholipid metabolite profile.

Research conclusions

The authors found that the A/A genotype at PNPLA3 rs139051 exerts an up-regulatory effect on serum phospholipids of lysophosphatidylcholine (LPC) and lysophosphatidylcholine plasmalogen (LPCO), which are associated with low-grade lobular inflammation of NAFLD.

Research perspectives

These experimental observations relating to NAFLD patients revealed that an increase in LPCs and LPCOs significantly correlated with an attenuation of hepatic inflammation. However, the pathological characteristics other than hepatic inflammation displayed no association with either of these phospholipid metabolites.