The association of non-alcoholic fatty liver index, plasma metal levels, and genetic susceptibility using genome-wide type analysis.

BACKGROUND & AIMS: This study aimed to explore the relationship between heavy metal exposure and the occurrence of non-alcoholic fatty liver disease (NAFLD), an area with conflicting existing research and unexplored genetic implications.

METHODS

Data from 444 individuals working in metal industries and 767 people working in non-metal-related jobs were analyzed. Patients with viral hepatitis or alcoholism were excluded. The data included physical examination, biochemical data, and plasma concentrations of six different metals. We utilized the genomic database of the Taiwan Biobank to conduct the GWAS. Further analysis was performed using multivariable logistic regression and an interaction study.

RESULTS

Patients with NAFLD had higher plasma concentrations of Se, Zn, Cu, and Pb, although none reached statistical significance. The Cu level was significant in the multiple logistic regression analysis. Our findings revealed a significant association between NAFLD and only two SNPs: rs879304 in the MAGI2 gene showed A > G OR = 0.67 (95% CI: 0.52, 0.86), and rs80040482 in the SNX19 gene C > A (OR = 2.21, 95% CI: 1.39, 3.49). We also examined 25 SNPs from various genes previously linked to NAFLD. However, none of these showed any significant relationship with NAFLD in multivariable logistic regression and interaction analyses.

CONCLUSIONS

Our findings suggest that plasma copper levels were associated with NAFLD. In addition, exploratory analyses suggested that the association between blood copper and NAFLD may vary according to genetic variants in MAGI2 and SNX19. Given the cross-sectional design, these findings should be interpreted as associations only and require confirmation in longitudinal and mechanistic studies.