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

doi:10.4254/wjh.v12.i12.1228

Validation of genetic variants associated with metabolic dysfunction-associated fatty liver disease in an ethnic Chinese population

World J Hepatol. 2020 Dec 27;12(12):1228-1238. doi: 10.4254/wjh.v12.i12.1228.

Authors

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore 119228, Singapore.
² Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
³ Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828, Singapore.
⁴ Department of Surgery, National University Health System, Singapore 119228, Singapore.

Abstract

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.

Keywords: Body mass index; Genotyping; Hepatic steatosis; Hypertriglyceridemia; Metabolic dysfunction-associated fatty liver disease; Non-alcoholic steatohepatitis; PNPLA3; Single nucleotide polymorphism; Waist-hip ratio, Screening.