PNPLA3 and SAMM50 variants are associated with lean nonalcoholic fatty liver disease in Asian population.

Abstract

Introduction and objectives: Lean adults with nonalcoholic fatty liver disease (NAFLD) have a higher risk of metabolic syndrome than lean controls. The study aimed to investigate the clinical and genetic features of lean NAFLD which remain unclear in Asian populations.

Materials and methods: This was a genetic cohort study conducted in the HAVO Health Exam Clinic in 2020-2021 in Taiwan. Adults with a body mass index less than 24 kg/m² were enrolled. Fatty liver was defined by ultrasonography. The candidate gene approach was based on the library of the NHGRI-EBI website. After removing duplication and nonsignificant variants, rs738409 in the PNPLA3 gene and rs3761472 in the SAMM50 gene were chosen. Multiple logistic regression models and receiver operating characteristic (ROC) curves were used.

Results: A total of 1652 lean controls and 602 lean NAFLD patients were enrolled. The average age was 43.8 ± 11.5 years. Lean NAFLD subjects were older and had a higher percentage of metabolic syndrome (case vs. control: 10.5 % vs. 1.5 %). The GG genotypes of PNPLA3 rs12483959 (OR: 3.06; 95% CI: 2.15-4.37) and SAMM50 rs3761472 (OR: 2.90; 95% CI: 2.04-4.14) had a higher risk of fatty liver after adjusting for BMI and metabolic syndrome. The areas under the ROC curve for PNPLA3 rs738409 and SAMM50 rs3761472 in the detection of lean NAFLD were 0.859 (95%CI: 0.841, 0.877) and 0.860 (95%CI: 0.843, 0.877), respectively.

Conclusions: PNPLA3 rs738409 and SAMM50 rs3761472 gene polymorphisms are associated with a higher risk of fatty liver in lean individuals independent of BMI and metabolic syndrome in Asian populations.