Abstract:Objective To investigate the relationship between serum manganese (Mn) levels and non-alcoholic fatty liver disease (NAFLD) in individuals of different genders. Methods Participants aged 18 years or older from the National Health and Nutrition Examination Survey (NHANES) database between 2017 and 2018 were selected, excluding those who lacked ultrasonic liver transient elastography data, serum Mn data, and individuals with hepatitis B, hepatitis C, or significant alcohol consumption. The included population (n=4 294) was divided into NAFLD group (n=2 708) and the non-NAFLD group (n=1 586) according to whether participant had NAFLD or not. Serum Mn levels were quantitatively measured by inductively coupled plasma dynamic reaction cell mass spectrometry. Age, gender, race, marital status, education, family income-to-poverty ratio (FMPIR), body mass index (BMI), smoking, alcohol consumption, diabetes, hypertension, hyperlipidemia, and serum Mn levels were compared between the two groups. Continuous variables were compared by t-tests or Wilcoxon rank-sum tests, while categorical variables were compared by chi-square tests. Males and females were respectively divided into four groups (Q1-Q4) according to their Mn levels by quartile method. Multivariate logistic regression, restricted cubic spline regression analysis, interaction, and subgroup analysis were performed to explore the risk association between serum Mn and NAFLD in different genders. Results Serum Mn level in the NAFLD group was significantly higher than that in the non-NAFLD group［9.06 (7.25, 11.38)μg/L vs 9.33 (7.54, 11.52) μg/L, Z=2.815, P=0.005］. After adjusting for age, race, education, marital status, FMPIR, BMI, smoking, alcohol consumption, diabetes mellitus, hypertension and hyperlipidemia as covariates, male participants in the serum Mn Q3 group (OR=1.575; 95%CI: 1.193-2.087) and female participants in the serum Mn Q4 group (OR=1.725; 95%CI: 1.313-2.269) had significantly increased risks of developing NAFLD when compared to those in the Q1 group (P＜0.01). There was a significant positive dose-response relationship between serum Mn and the risk of NAFLD for both males and females (P＜0.01), with a nonlinear relationship for males (P_non-linear＜0.01) and a linear relationship for females (P_non-linear=0.818）. Significant interactions were observed between serum Mn and race in males, and between serum Mn and hypertension in females. Conclusion Serum Mn levels in both males and females are significantly associated with the risk of NAFLD.