Association of plasma manganese and MnSOD rs4880 polymorphism with nonalcoholic fatty liver disease

BACKGROUND AND AIM: Manganese is both an essential micronutrient and a known toxicant, and plays crucial roles in normal metabolism. However, few researchers have focused on the association between manganese and nonalcoholic fatty liver disease (NAFLD), and it is unclear whether this association differs according to manganese superoxide dismutase (MnSOD) genetic variations. We aimed to explore the association between plasma manganese and NAFLD as well as whether the association could be modified by MnSOD polymorphisms. METHODS: We performed a 1:1 matched case-control study in 1838 Chinese Han subjects, who were determined according to the NAFLD diagnosis and treatment guidelines of the Chinese Medical Association. Plasma manganese levels were detected by inductively coupled plasma mass spectrometry, and MassArray system was applied for MnSOD rs4880 polymorphism genotyping. RESULTS:The medians of plasma manganese concentrations were 3.80 and 3.38 μg/L for controls and NAFLD, respectively. After multivariable adjustment, the correlation between plasma manganese levels and NAFLD still existed and showed a negatively correlated dose-effect relationship. The ORs (95% CIs) of NAFLD across quartiles of plasma manganese were 1.00 (reference), 0.78 (0.58–1.07), 0.58 (0.41–0.81), 0.55 (0.39–0.77) (P-trend 0.001). For each SD increment in plasma manganese, the risk of NAFLD decreased by 20% (adjusted OR = 0.80, 95% CI: 0.71–0.91). In the restrict cubic spline analysis, we observed the odds of NAFLD were decreased with the increment of manganese concentration and reached a plateau at around 4.50 µg/L. Compared with the rs4880 TT genotype, the associations between CT, CC, CT + CC genotypes and NAFLD were not significant, and we did not observe interaction effects of plasma manganese and MnSOD rs4880 polymorphisms on NAFLD. CONCLUSIONS:Our results suggested a significantly negative association between plasma manganese levels and NAFLD, and the association was not modified by the MnSOD rs4880 polymorphism. KEYWORDS: Heavy metals, Epidemiology, Obesity and metabolic disorders