Association Between ADH1B rs1229984 Genetic Polymorphism and Hepatic Steatosis Assessed by CT Attenuation: A Mediation Analysis of Central Obesity in MASLD
Chih‐Wen Wang, Chung‐Feng Huang, Ming‐Lun Yeh, Po‐Cheng Liang, Tyng‐Yuan Jang, Yu‐Ju Wei, Ming‐Yen Hsieh, Chao‐Kuan Huang, Nai‐Jen Hou, Yi‐Hung Lin, Tusty‐Jiuan Hsieh, Jee‐Fu Huang, Chia‐Yen Dai, Wan‐Long Chuang, Ming‐Lung Yu, Che‐Hong ChenABSTRACT
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.