Case Control Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2024; 16(3): 366-378
Published online Mar 27, 2024. doi: 10.4254/wjh.v16.i3.366
Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus
Kanuengnit Choochuay, Punna Kunhapan, Apichaya Puangpetch, Sissades Tongsima, Pornpen Srisawasdi, Abhasnee Sobhonslidsuk, Somnuek Sungkanuparph, Mohitosh Biswas, Chonlaphat Sukasem
Kanuengnit Choochuay, Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Kanuengnit Choochuay, School of Pharmacy, Walailak University, Nakhon Si Thammarat 80161, Thailand
Kanuengnit Choochuay, Apichaya Puangpetch, Chonlaphat Sukasem, Laboratory for Pharmacogenomics, Division of Pharmacogenomics and Personalized Medicine, Somdech Phra Debaratana Medical Center, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Punna Kunhapan, Department of Medical Sciences, Ministry of Public Health, Nonthaburi 11000, Thailand
Sissades Tongsima, National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, Pathum Thani 12120, Thailand
Pornpen Srisawasdi, Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Abhasnee Sobhonslidsuk, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Somnuek Sungkanuparph, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan 10540, Thailand
Mohitosh Biswas, Department of Pharmacy, University of Rajshahi, Rajshahi 6205, Bangladesh
Chonlaphat Sukasem, Pharmacogenomics Clinic, Bumrungrad Genomic Medicine Institute, Bumrungrad International Hospital, Bangkok 10110, Thailand
Chonlaphat Sukasem, Research and Development Laboratory, Bumrungrad International Hospital, Bangkok 10110, Thailand
Chonlaphat Sukasem, MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, United Kingdom
Chonlaphat Sukasem, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
Author contributions: Choochauy K performed the majority of experiments and wrote the manuscript; Sukasem C conceptualized, validated and designed the study and corrected the manuscript; Kunhapan P, Puangpetch A, and Tongsima S involved in analytical tools; Srisawasdi P participated to the collection of the human material and clinical data; Sobhonslidsuk A and Sungkanuparph S served as scientific advisors and participated in the collection of human materials; Biswas M critically reviewed the manuscript to improve overall clarity and quality; Sukasem C was the guarantor.
Supported by the Faculty of Medicine, Ramathibodi Hospital, Mahidol University.
Institutional review board statement: The study was approved by the ethics committee of the Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Bangkok, Thailand) (COA. MURA2019/645). All study procedures were conducted in accordance with the 1964 Helsinki Declaration.
Informed consent statement: In this investigation, genomic material was isolated from residual specimens of the study subjects, demonstrating minimal risk to patients and participant consent was not necessary.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Open-Access: This article is an open-access article that 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chonlaphat Sukasem, PhD, Professor, Laboratory for Pharmacogenomics, Division of Pharmacogenomics and Personalized Medicine, Somdech Phra Debaratana Medical Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. chonlaphat.suk@mahidol.ac.th
Received: November 1, 2023
Peer-review started: November 1, 2023
First decision: December 5, 2023
Revised: January 9, 2024
Accepted: February 8, 2024
Article in press: February 8, 2024
Published online: March 27, 2024
Processing time: 146 Days and 23.8 Hours
Abstract
BACKGROUND

The prevalence of metabolic-associated fatty liver disease (MAFLD) is a growing public health issue in people living with human immunodeficiency virus (PLWH). However, the pathophysiology of MAFLD is still unknown, and the role of genetic variables is only now becoming evident.

AIM

To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.

METHODS

The study employed transient elastography with a controlled attenuation parameter ≥ 248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand. Candidate single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan® MGB probe 5' nuclease assays for seven MAFLD-related genes. Statistical analyses included SNP frequency analysis, Fisher's Exact and Chi-square tests, odds ratio calculations, and multivariable logistic regression.

RESULTS

The G-allele carriers of PNPLA3 (rs738409) exhibited a two-fold rise in MAFLD, increasing by 2.5 times in MAFLD with human immunodeficiency virus infection. The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times (P = 0.001) more significant chance of developing aberrant triglyceride among PLWH.

CONCLUSION

The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

Keywords: PNPLA3; LEP; Metabolic-associated fatty liver disease; People living with HIV; Thai

Core Tip: The prevalence of metabolic-associated fatty liver disease (MAFLD) in people living with human immunodeficiency virus (PLWH) is increasing, becoming a public health concern. The current evidence suggests that aspartate transaminase, fasting plasma glucose, triglyceride, total cholesterol, low-density lipoprotein, and the genetic factors PNPLA3 rs738409 and LEP rs7799039 indicate genetic susceptibility for PLWH, leading to improvements in MAFLD.