Abstract: Objective To investigate the prevalence of metabolic-associated fatty liver disease (MAFLD) in Urumqi, and to explore the association of the methylation of PNPLA3 and FABP1 genes with the incidence of MAFLD by comparing the methylation levels of PNPLA3 and FABP1 genes between MAFLD patients and normal people. Methods The clinical data of the population undergoing physical examination in the First Affiliated Hospital of Xinjiang Medical University from January to March 2022 were retrospectively analyzed. 15 patients with MAFLD were recruited as the case group, and 15 healthy people without previous history of liver diseases were matched at the same time as the control group. Methylation specific PCR (MSP) method was used to detect the methylation of PNPLA3 and FABP1 genes. Point-biserial correlation was used to analyze the correlation between clinical data and the genes expression. Results A total of 1081 cases (33.84%) in 3194 physical examination subjects were diagnosed as MAFLD, including 698 (64.57%) males, 383 (35.43%) females, and 424 cases (39.22%) with age of 40 to 50 years old, the differences were statistically significant (P<0.001). There were 2 cases (13.33%) in the case group and 10 cases (66.67%) in the control group had PNPLA3 gene hypermethylation, the difference was statistically significant (χ²=6.806, P=0.009). Similarly there were 5 cases (33.33%) in the case group and 12 cases (80.00%) in the control group had FABP1 gene hypermethylated status, the difference was statistically significant (χ²=4.887, P=0.027). The methylation status of PNPLA3 gene was negatively correlated with the levels of fasting blood glucose (FPG) (r=-0.385, P<0.05), triglyceride (TG)(r=-0.584, P<0.05), and high density lipoprotein (HDL-C)(r=0.651, P<0.001). The methylation status of FABP1 gene was negatively correlated with the serum levels of urea (UA) (r=0.407, P<0.05), FPG (r=0.416, P<0.05), TG (r=0.565, P<0.05), total cholesterol (TC) (r=0.515, P<0.05), aspertate aminotransferase (AST) (r=-0.416, P<0.05), alanine aminotransferase (ALT) (r=0.473, P<0.05), whereas positively correlated with the level of HDL-C (r=0.487, P<0.05). Conclusion The prevalence of MAFLD in Urumqi is the highest in China. The methylation status of PNPLA3 and FABP1 genes promoter region in blood cells of patients with MAFLD was significantly decreased, and was correlated with FPG, TG, TC, UA, AST, ALT, HDL-C and apolipoprotein B, which is one of the important mechanisms for the occurrence and development of MAFLD.

Key words: Metabolism-related fatty liver disease, Methylation, PNPLA3 gene, FABP1 genes, Correlation analysis