BACKGROUND/AIM The incidence and significance of HFE mutations (C282Y, H63D, and S65C) in nonalcoholic fatty liver disease (NAFLD) has not been investigated in Korea.

METHODS Mutation analysis of HFE gene and measurement of blood iron indices were carried out in 125 NAFLD patients and 221 controls.

RESULTS Neither C282Y nor S65C gene mutations were detected. The prevalence of the H63D mutation was higher in the NAFLD group (14.4%) than in the controls (7.2%) (P=0.032). The estimated odds ratio (OR) of NAFLD for H63D mutations was 3.09 (P=0.008) by multivariate analysis, and age, gender, obesity, diabetes mellitus, and hypercholesterolemia were independent variables associated with NAFLD. However, in the multivariate analysis containing interaction of the types of HFE mutations and gender, the prevalence of the H63D mutation was significantly higher in the male NAFLD group than in the male control group (OR=5.51, P=0.007); the difference of the prevalence between the NAFLD and the control group in females was not significant. The NAFLD patients with H63D mutations had higher levels of TS than those with the wild type (OR=3.14, P=0.048) by the multivariate analysis. A higher TS was significantly associated with the lower body mass index only in the male NAFLD group by multivariate analysis (OR=0.67, P=0.002).

CONCLUSIONS The presence of H63D mutations was an independent factor associated with NAFLD and elevated TS. Therefore, the H63D mutation may increase susceptibility to NAFLD probably associated with peripheral iron overload, especially in males.