Association Between ADH1B rs1229984 Genetic Polymorphism and Hepatic Steatosis Assessed by CT Attenuation: A Mediation Analysis of Central Obesity in MASLD.

BACKGROUND AND AIMS: ADH1B genetic variants have recently emerged as a novel genetic determinant of metabolic dysfunction-associated steatotic liver disease (MASLD); however, their clinical significance in Asian populations is unclear.

METHODS

We used multivariable logistic regression to evaluate the association between ADH1B genetic variants and MASLD risk and mediation analysis to quantify the direct effects of ADH1B polymorphisms and the indirect effects mediated by central obesity.

RESULTS

The AA genotype was associated with lower waist circumference (81.9 ± 11.0 cm) and higher liver computed tomography (CT) attenuation (58.7 ± 9.3 HU) compared with the AG (84.1 ± 11.1 cm; 56.9 ± 9.4 HU) and GG (84.7 ± 9.6 cm; 54.0 ± 9.8 HU) genotypes. Compared with the AA genotype, the GG and AG genotypes were associated with a higher MASLD risk by both ultrasonography (GG: OR = 3.97, 95% CI: 1.68-9.38, p = 0.002; AG: OR = 1.97, 95% CI: 1.16-3.35, p = 0.012) and CT criteria (GG: OR = 3.98, 95% CI: 1.75-9.02, p = 0.001; AG: OR = 2.33, 95% CI: 1.47-3.69, p < 0.001). Waist circumference mediated 17.4% and 30.2% of the associations between the ADH1B dominant genotype and MASLD by CT liver-to-spleen attenuation ratio < 1.0 and ultrasonography. Waist circumference accounted for 39.7% of the association between the ADH1B dominant genotype and hepatic steatosis assessed by liver CT attenuation.

CONCLUSIONS

ADH1B variants were associated with MASLD, and mediation analysis demonstrated a statistical mediation pattern involving waist circumference that was consistent with a hypothesized adipose-liver pathway.