Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

doi:10.4254/wjh.v16.i3.366

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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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.

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

ARTICLE HIGHLIGHTS

Research background

Metabolic-associated fatty liver disease (MAFLD), which is characterized by hepatocyte fat accumulation, poses substantial health risks; it affects a significant number of people globally, especially those living with obesity, diabetes, dyslipidemia, hypertension, and metabolic syndrome. Despite its prevalence, the precise mechanisms underlying MAFLD, which involve factors including viral hepatitis, human immunodeficiency virus (HIV), antiretroviral treatment, and genetics, remain unclear.

Research motivation

MAFLD is prevalent among individuals with HIV, with rates ranging from 40% to 55%; it is influenced by both antiretroviral medications and specific genetic variants. Notably, the PNPLA3 rs738409 variant, a genetic factor, plays a significant role in the development of MAFLD.

Research objectives

The present investigation sought to assess the correlation between gene polymorphisms and MAFLD in individuals living with HIV.

Research methods

We employed transient elastography and set a threshold for the controlled attenuated parameter at ≥ 248 dB/m for the identification of MAFLD. All participants underwent genotyping for candidate single-nucleotide polymorphisms.

Research results

Individuals carrying the G-allele of PNPLA3 (rs738409) demonstrated a two-fold increased risk of developing MAFLD; this risk rose to 2.5 times in cases of MAFLD with HIV infection. The clinical characteristics and genetic profiles suggested that carriers of the A-allele of LEP rs7799039 had a nine-fold higher likelihood of developing abnormal triglyceride levels among individuals living with HIV.

Research conclusions

The present research reveals a connection between PNPLA3 rs738409 and LEP rs7799039 and MAFLD in individuals with HIV.

Research perspectives

Genetic factors play a crucial role in the pathophysiology of MAFLD. In upcoming research, targeting the PNPLA3 gene in clinical trials may emerge as a promising direction for precision medicine in the treatment of MAFLD.