Association of APOC3 promoter variants with hypertriglyceridemia and metabolic dysfunction-associated steatotic liver disease (MASLD) in a Thai cohort

Apolipoprotein C-III (APOC3) regulates triglyceride metabolism by inhibiting lipoprotein lipase activity and reducing the clearance of triglyceride-rich lipoproteins. We investigated the associations of APOC3 promoter polymorphisms (rs2854116 and rs2854117) with hypertriglyceridemia and metabolic dysfunction-associated steatotic liver disease (MASLD) in a Thai cohort. This cross-sectional study included 276 Thai adults from a MASLD case-control cohort. MASLD was defined using controlled attenuation parameter (CAP ≥ 248 dB/m) measured by transient elastography. APOC3 rs2854116 and rs2854117 were genotyped, and associations with hypertriglyceridemia and MASLD were evaluated using logistic regression under a prespecified additive genetic model. Sensitivity analyses stratified by and adjusted for MASLD status were performed. Exploratory haplotype analyses were also conducted. Under the additive model, rs2854116 was associated with hypertriglyceridemia in crude (OR 1.58 per T allele, 95% CI 1.08–2.33; p = 0.019) and adjusted analyses (OR 1.58, 95% CI 1.06–2.36; p = 0.025; FDR-adjusted p = 0.050), meeting the prespecified FDR threshold for the primary hypothesis family. The association remained significant after adjustment for MASLD status (OR 1.61, 95% CI 1.08–2.41; p = 0.020) and was consistent across MASLD strata ( p for interaction = 0.61). The minor T allele was more frequent among participants with hypertriglyceridemia than among normotriglyceridemic controls (54.5% vs. 43.7%; OR 1.54, 95% CI 1.06–2.24; p = 0.022). Neither rs2854116 nor rs2854117 was associated with MASLD. Exploratory haplotype analyses likewise showed no consistent association with MASLD. APOC3 rs2854116 was associated with hypertriglyceridemia in this Thai cohort, supporting its role in triglyceride metabolism. In contrast, no clear evidence was found for an association between APOC3 variants and MASLD. Because the cohort was selected according to MASLD status, potential selection or collider bias cannot be excluded, and these findings require confirmation in larger, population-based Thai cohorts.