Background and purpose: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction worldwide. Genetic factors are believed to affect the development of NAFLD. This study was conducted to evaluate the interaction of weight loss and MTHFR polymorphism on NAFLD characteristics.

Materials and methods: A single-arm trial was performed in 50 patients. They received a weight loss diet for 6 months. Anthropometric parameters, liver enzymes, dietary intakes, and physical activity were measured at first, and the end of months 3 and 6. Lipid profile, homocysteine, malondialdehyde, TNF-α, IL-6, and cytokeratin 18 were measured at baseline and at the end of the study. C677T and A1298C MTHFR gene polymorphisms were assessed in all patients using PCR-RFLP and Tetra-ARMS methods, respectively.

Results: Forty four patients completed the study protocol. According to MTHFR polymorphism the patients were classified as (CC) and (AC) group (n= 35), and (CT+TT) and (AC) group (n= 9). After 3 and 6 months, weight loss occurred equally in both groups. In CC genotype, fasting blood glucose
(P= 0.012), total cholesterol (P= 0.001), and LDL (P=0.004) decreased significantly after 6 months. In those with CT+TT genotype, after 6 months, 6.6% weight loss occurred but it could not significantly reduce liver enzymes and the patients’ homocysteine levels were higher than normal range.

Conclusion: In this study, no significant reduction in liver enzymes was observed in the CT+TT sub group, therefore, MTHFR gene polymorphisms should be considered in NAFLD management.