Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is related to unhealthy habits, mainly to unfavorable dietary profiles. MTHFR gene encodes MethyleneTetraHydroFolate Reductase, a regulatory enzyme whose polymorphisms are associated with hyperhomocysteinemia. Among polymorphisms, C677T, a thermolabile form, but not A1298C, thermostable, was associated with fatty liver and insulin resistance.
Aim: to investigate if NAFLD, in subjects referred for nutritional assessment and counselling, has any difference of prevalence and severity when associated with isolated MTHFR A1298C polymorphism and hyperhomocysteinemia.
Patients and methods: 94 subjects, age 55.65 ± 15.43 years, BMI 27.88 ± 5.17 kg/m2, 26 with MTHFR Wild type genotype (1298AA) and 68 with MTHFRA1298C single polymorphism were studied: of them, 35 were homozygous (MTHFR1298CC), 33 were heterozygous (MHTFR 1298AC). Insulin resistance was assessed by HOMA-IR, NAFLD by UltraSound Brigh-Liver-Score (BLS).
Results: MTHFR subgroups (wild and A1298C single polymorphism) were not different for age, gender, dietary profile and BMI. In NAFLD, MTHFR 1298AC (heterozygous) vs. homozygous wild genotype (MTHFR 1298AA) patients had more severe NAFLD (BLS: 1.12 ± 1.14 vs. 0.54 ± 0.76, p < 0.029), greater insulin resistance (HOMA 3.20±2.35 vs. 2.12 ± 1.12; p < 0.036), higher AST and gammaGT.
Conclusions: MTHFR1298AC gene heterozygous polymorphisms can be weakly predictive for NAFLD severity. This mutation occurs frequently in populations with low prevalence of overall mortality and of atherosclerosis-associated disease: it could have maintained and maintain its persistence by an heterozygosis advantage mechanism, within significant adherence to healthy nutritional profiles. Interactions of nutrition, genetics and health are a part of the aging process throughout the life span and a greater consideration to the genetic characteristics of populations and individuals is warranted.