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

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 , , , , , , , , , and 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 60.8 kg, 95%CI: 48.5-73.1, < 0.001 and 26.9 kg, 95%CI: 23-40.8 23.3 kg 95%CI: 19-27.6, < 0.001 respectively). The prevalence of diabetes mellitus in patients was 40.3% and 20.8% in controls ( = 0.011). Patients had higher mean triglycerides than controls ( < 0.001). GG was more likely to be associated with MAFLD (43.4% CC 69.7% GG, = 0.017, and 44.8% CG 69.7% GG, = 0.022). In multivariable analysis, hypertriglyceridemia (odds ratio [OR]: 2.04 95%CI: 1.3-3.1, = 0.001), BMI (OR: 1.2 95%CI: 1.1-1.4, < 0.001) and GG (OR: 3.4 95%CI: 1.3-9.2, = 0.014) were associated with MAFLD (area under the receiver operating characteristic curve of 0.823).

CONCLUSION

Among the Chinese population of Singapore, homozygous GG allele is a strong predictor of MAFLD, whereas , , , , , and are not significantly associated. Hypertriglyceridemia, high BMI, and GG are independent predictors of MAFLD.