Abstract
BACKGROUND AND AIMS: Manganese (Mn) deficiency and intoxication may affect nonalcoholic fatty liver disease (NAFLD) risk differently. We aimed to explore the association between blood Mn and NAFLD in an area with high Mn exposure in drinking water. METHODS: We conducted a case-control study among 1407 patients with NAFLD and 1774 sex- and age-matched healthy controls in a physical examination population in Zhoushan hospital, Zhejiang province in China. We used the restricted cubic splines method to investigate the dose-response relationship. Logistic regression models were applied to determine the risk of NAFLD, and severity of NAFLD. RESULTS: The blood Mn concentration was higher in the NAFLD group than in the control group in women (16.1 ± 6.2 μg/L vs. 14.7 ± 6.4 μg/L, P = 0.022) and men (14.5 ± 6.3 μg/L vs. 13.6 ± 6.8 μg/L, P < 0.001). We found an inverted L shape relationship between blood Mn and NAFLD in both women and men. Compared to the lowest quartile, the adjusted odds ratio (OR) and 95% confidence interval (CI) of NAFLD for the highest quartile group was 1.646(1.222,2.217), 1.494(1.082,2.061), and 3.146(1.285,7.701) for the total population, men, and women. The positive relationship was only observed in those with fibrosis-4 score < 1.30 and normal alanine transaminase. Stratified analysis showed an interaction between smoking (P = 0.073), alcohol drinking (P = 0.013), and Mn, with a more prominent effect on the NAFLD in the never-smokers (OR = 2.153, 95% CI 1.408-3.290) and drinkers (OR = 2.596, 95% CI 1.608-4.191). CONCLUSION: Higher blood Mn is associated with an elevated NAFLD risk in the high Mn exposure areas, especially in nonsmokers and drinkers. Further studies are needed to verify this result in the areas with high Mn exposure.