Polymorphisms 677C > T and 1298A > C in the MTHFR gene and homocysteine levels in patients with non-alcoholic fatty liver disease as a component of the ontological model

Abstract

Objective — to systematize literature data on the presence of 677C > T and 1298A > C polymorphisms in the MTHFR gene and homocysteine levels in patients with non‑alcoholic fatty liver disease (NAFLD); to calculate the frequencies 677C > T and 1298A > C polymorphisms combinations in the MTHFR gene and their impact on NAFLD development; to compare homocysteine levels in patients with and without NAFLD.
 Materials and methods. The analysis has been performed for the results of investigation of 49 patients, from them 17 subjects with NAFLD and 32 without it. Clinical, laboratory, statistical and ontological methods were used in the study. The MTHFR 677C > T and MTHFR 1298A > C polymorphisms in the MTHFR gene were investigated with the use of real time polymerase chain reaction (RT‑PCR) technique. Homocysteine levels were determined with chemiluminescent immunoassay with reference values 3.7 — 13.9 µmol/L. Multiple logistic regression method was used to evaluate the effects 677C > T and 1298A > C polymorphisms in the MTHFR gene on NAFLD development.
 Results. The variant of combination of 667С/С/1298А/А polymorphisms in the MTHFR gene (absence of mutation) was reveled in 6 (12 %) persons, that showed a widespread prevalence of variants with the presence of mutations. The correlation between variants of 677C > T and 1298A > C polymorphism in the MTHFR gene has been established (r = 0.429; p < 0.05). The results of multiple logistic regression demonstrated absence of the significant effects of 677C > T and 1298A > C polymorphisms in the MTHFR gen on NAFLD development (p > 0.05). Comparison of the homocysteine levels in patients with and without NAFLD didn’t reveal significant difference (р > 0.05), as well as comparison in the groups with combinations of 677C > T and 1298А > С polymorphisms in the MTHFR gen (р > 0.05). This can be explained by the fact that NAFLD group consisted of manly young patients without hypertension, type 2 diabetes mellitus and severe liver fibrosis.
 Conclusions. Ontological systematization of the scientific data on NAFLD revealed that 677C > T and 1298A > C polymorphisms in the MTHFR gen are pathogenetically associated with the significant increase in homocysteine levels as a marker of cardiovascular pathology. Giving the multifactorial nature of hyperhomocysteinemia and wide spread of 677C > T and 1298A > C polymorphisms in the MTHFR gen in population, it seems to be impractical to use genetic investigations for MTHFR gen polymorphism in NAFLD patients routinely, but only for the purpose of differential diagnosis of hyperhomocysteinemia.