(PTFS12-04-25) MTHFR C677T Polymorphism and Red Blood Cell Folate Concentrations Modifying the Risks of Hepatic Steatosis: A Taiwan Case-Control Study

Objectives: The interaction between folate status and the 5-methylenetrahydrofolate reductase (MTHFR) genetic polymorphism on the risks of nonalcoholic fatty liver (NAFL) has not been well elucidated. The study aimed to investigate the relationship between red blood cell (RBC) folate status and MTHFR C677T polymorphism on NAFL risk.

Methods: The cross-sectional case-control study was conducted in one regional hospital during the years 2020 and 2022 using the sonographic diagnosis of hepatic steatosis (HS). Habitual dietary intakes were assessed using a validated quantitative FFQ through a face-to-face interview. MTHFR rs1801133 (C677T, C to T substitution) polymorphism and blood metabolic disorder factors were analyzed.

Results: A total of 373 subjects were recruited, with 219 HS cases and 154 non-HS controls. The distribution of the MTHFR C677T polymorphism did not significantly differ between the HS and control groups (p=0.999). The 3^rd tertiles of RBC folate showed higher odds ratios (OR) of NAFL risk than the 1^st tertile but were not significant. For those with 677CT/TT genotypes and RBC folate >405 ng/ml, the risk of NAFL significantly increased compared to 677CC genotypes (OR=3.475, 95% CI=1.369-8.819, p=0.029). Among 677CC genotype individuals, those with RBC folate < 405 ng/ml had a higher risk of NAFL compared to those with RBC folate >405 ng/ml (OR=2.520, 95% CI=1.086-5.846, p=0.031).

Conclusions: With higher RBC folate levels, the MTHFR 677CT/TT genotype increased NAFL risk compared to 677CC cases. In MTHFR 677CC cases, higher RBC folate levels reduced NAFL risk compared to lower RBC folate levels.

Funding Sources: The Ministry of Health and Welfare-affiliated Taipei Hospital. The Ministration of Science and Technology, Taiwan, ROC.