Đa hình PNPLA3 rs738409 và hội chứng chuyển hóa ở người trưởng thành Việt Nam không mắc MASLD

Abstract

The PNPLA3 rs738409 (C>G) polymorphism drives hepatic steatosis, but its systemic effects in individuals without metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We investigated the association between this variant and metabolic syndrome (MetS) risk in a non-MASLD Vietnamese cohort. A cross-sectional analysis included 429 adults without MASLD or viral hepatitis undergoing routine health examinations. The rs738409 genotype (CC, GC, GG) was determined. MetS was defined as presenting ≥ 3 metabolic criteria. Multivariable logistic regression, adjusted for age, sex, and BMI, was performed to evaluate the genotypic effect on MetS risk. The G-allele frequency was 35.1%. The overall MetS prevalence was 11.4% (15.1% in CC, 8.5% in GC, and 10.0% in GG). In the dominant genetic model (GC+GG vs. CC), G-allele carriers exhibited a significantly reduced risk of MetS (adjusted OR = 0.40; 95% CI: 0.20 – 0.83, p = 0.014). Secondary continuous markers, including the triglyceride-glucose (TyG) index and hepatic transaminases, showed no significant variations across genotypes. The PNPLA3 rs738409 G allele is inversely associated with MetS risk in non-MASLD adults. This suggests a metabolic dissociation phenomenon, wherein the variant does not precipitate systemic insulin resistance in the absence of steatosis.