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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Validation of genetic variants associated with metabolic dysfunction-associated fatty liver disease in an ethnic Chinese population
Guan Huei Lee, Wah Wah Phyo, Wai Mun Loo, Raymond Kwok, Taufique Ahmed, Asim Shabbir, Jimmy So, Calvin Jianyi Koh, Juanda Leo Hartono, Mark Muthiah, Kieron Lim, Poh Seng Tan, Yin Mei Lee, Seng Gee Lim, Yock Young Dan
Guan Huei Lee, Wai Mun Loo, Calvin Jianyi Koh, Juanda Leo Hartono, Mark Muthiah, Kieron Lim, Poh Seng Tan, Yin Mei Lee, Seng Gee Lim, Yock Young Dan, Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore 119228, Singapore
Guan Huei Lee, Wah Wah Phyo, Seng Gee Lim, Yock Young Dan, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Raymond Kwok, Taufique Ahmed, Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828, Singapore
Asim Shabbir, Jimmy So, Department of Surgery, National University Health System, Singapore 119228, Singapore
Author contributions: Lee GH was involved in the conception and design of the study, data collection and analysis, drafting and revision of the manuscript; Phyo WW was involved in the data collection and analysis; Loo WM was involved in the drafting and revision of the manuscript; Kwok R, Ahmed T, Shabbir A, So J, Koh CJ, Hartono JL, Muthiah M, Lim K, Tan PS, Lee YM, Lim SG, and Dan YY contributed to the data collection and revision of the manuscript.
Supported by National University Health System, No. NUHSRO/2013/226/CRG/08.
Institutional review board statement: The study was approved by the Institutional Review Board.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Data sharing statement: No additional data 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 NonCommercial (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/ Corresponding author: Guan Huei Lee, MBBS, PhD, Doctor, Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Singapore 119228, Singapore. mdcleegh@nus.edu.sg
Received: July 7, 2020
Peer-review started: July 9, 2020
First decision: September 11, 2020
Revised: September 28, 2020
Accepted: October 15, 2020
Article in press: October 15, 2020
Published online: December 27, 2020
BACKGROUND
Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease (MAFLD).
AIM
To study the association of single nucleotide polymorphisms (SNPs), previously identified in Western populations, with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk factors.
METHODS
A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography, magnetic resonance imaging, or controlled attenuation parameter score. Subjects were recruited from two tertiary hospitals. Genetic alleles such as NCAN, GCKR, LYPLAL1, PNPLA3, PPP1R3B, FDFT1, COL13A1, EFCAB4B, PZP, and TM6SF2 were genotyped using the TaqMan® Predesigned SNP Genotyping Assay.
RESULTS
Weight and body mass index (BMI) were 1.2-times higher in patients (70.6 kg, 95% confidence interval [CI]: 57.1-84.1 vs 60.8 kg, 95%CI: 48.5-73.1, P < 0.001 and 26.9 kg, 95%CI: 23-40.8 vs 23.3 kg 95%CI: 19-27.6, P < 0.001 respectively). The prevalence of diabetes mellitus in patients was 40.3% and 20.8% in controls (P = 0.011). Patients had higher mean triglycerides than controls (P < 0.001). PNPLA3 GG was more likely to be associated with MAFLD (43.4% CC vs 69.7% GG, P = 0.017, and 44.8% CG vs 69.7% GG, P = 0.022). In multivariable analysis, hypertriglyceridemia (odds ratio [OR]: 2.04 95%CI: 1.3-3.1, P = 0.001), BMI (OR: 1.2 95%CI: 1.1-1.4, P < 0.001) and PNPLA3 GG (OR: 3.4 95%CI: 1.3-9.2, P = 0.014) were associated with MAFLD (area under the receiver operating characteristic curve of 0.823).
CONCLUSION
Among the Chinese population of Singapore, PNPLA3 homozygous GG allele is a strong predictor of MAFLD, whereas LYPLAL1, GCKR, FDFT1, COL13A1, PZP, and TM6SF2 are not significantly associated. Hypertriglyceridemia, high BMI, and PNPLA3 GG are independent predictors of MAFLD.
Core Tip: A number of genetic variations (known as single nucleotide polymorphism, SNPs) are reportedly associated with metabolic dysfunction-associated fatty liver disease (MAFLD), mostly by studies from Europe and America. This study examined 10 of the most important SNPs in a Chinese population in Singapore, and found that 1 such variation, the PNPLA3 GG variation, is strongly linked to MAFLD, whereas the rest are not significantly associated. PNPLA3, together with high triglyceride and elevated body mass index, are found to be independent, strong predictors of MAFLD.
