Abstract
BACKGROUND AND AIM: Identifying the factors contributing to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), a lifestyle-related disease, is crucial for preventing future liver-related deaths. This study aimed to epidemiologically investigate factors, including single-nucleotide polymorphisms (SNPs) associated with alanine aminotransferase (ALT) levels >30 U/L and potential risk factors for liver fibrosis, in a general population cohort of patients with MASLD. METHODS: Among 1059 participants in the health checkup project, 228 who were diagnosed with MASLD were analyzed. Liver fat content and stiffness were measured using FibroScan, and 13 SNPs associated with non-alcoholic fatty liver disease (NAFLD) were measured in addition to other clinical parameters. RESULTS: In the multivariate analysis, male sex, younger age, and high triglyceride levels were significant risk factors for ALT levels >30 U/L (P-value < 0.05). Furthermore, among the 13 SNPs measured, only the GG genotypes of patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 and rs2896019 were significant risk factors for ALT levels >30 U/L (P-value 0.004 and 0.007). The GG genotypes of PNPLA3 rs738409 and rs2896019 had higher FibroScan-aspartate aminotransferase (FAST) and APRI scores than the CC + CG and TT + TG genotypes (P-value < 0.05). In addition, multivariate analysis revealed that the GG genotypes of rs738409 and rs2896019 were significant risk factors independent of cardiovascular metabolic risk for patients with MASLD (P-value 0.038 and 0.021). CONCLUSION: An individualized treatment approach is warranted for patients with MASLD due to the influence of various factors on its progression, including genetic factors and lifestyle diseases.