POLYMORPHISM OF FOLATE CYCLE GENES AND HYPERHOMOCYSTEINEMIA IN PATIENTS WITH METABOLICALLY ASSOCIATED FATTY LIVER DISEASE
DOI:
https://doi.org/10.11603/1811-2471.2025.v.i4.15812Keywords:
non-alcoholic fatty liver disease/metabolically associated fatty liver disease, insulin resistance, cardiovascular system, upper gastrointestinal tract, folate cycle gene polymorphism, homocysteine, B vitamins, methionineAbstract
SUMMARY. Genetic variations in genes encoding folate cycle enzymes are one of the main causes of homocysteine metabolism disorders and susceptibility to hyperhomocysteinemia (HHC).
The aim – to determine the characteristics of folate cycle gene polymorphism in patients with metabolically associated fatty liver disease (MAFLD) and its effect on HHC in these patients.
Material and Methods. 123 patients with MAFLD and insulin resistance (IR) were examined. Patients were divided into two groups depending on concomitant diseases. Group I included patients with MAFLD and cardiovascular system (CVS) damage (n=63), and group II consisted of 60 patients with MAFLD and upper gastrointestinal tract (UGIT) damage. The levels of B vitamins (B1, B3, B6, B9, B12), methionine, and homocysteine in blood serum were determined, and the polymorphism of folate cycle genes was assessed.
Results. Patients with MAFLD were found to have a deficiency of B vitamins in their blood serum against a background of HHC and a decrease in methionine levels. In group I, vitamin B1 levels decreased 2.8 times (p<0.001), while in group II patients, they decreased only 2.0 times (p<0.01); vitamin B3 levels decreased 2.5 times in patients in group I (p<0.001), while in patients in group II, they decreased 2.2 times (p<0.01). The same trend was found when assessing the levels of vitamins B9 and B12 in the examined patients (the most pronounced decrease was in patients from group I). In the vast majority of patients in both groups, a significant number of individuals were found to have low-functioning alleles in one, several, or all of the MTHFR, MTRR, and MTR genes.
Conclusions. In patients with MAFLD and IR combined with damage to the cardiovascular system and gastrointestinal tract, a deficiency of B vitamins and a decrease in methionine levels were found, accompanied by an increase in homocysteine levels in the blood serum of these patients.
In patients with MAFLD and IR combined with damage to the cardiovascular system, a genotype of low-functioning alleles (C/T + T/T) of the MTHFR-5,10 methylene tetrahydrofolate reductase gene (in 77.7% of cases – p<0.05) and a genotype (A/C + C/C) of the MTHFR-5,10 methylene tetrahydrofolate reductase gene (in 84.1% of those examined – p<0.05) were observed, while in patients with a combination of MAFLD and gastrointestinal tract damage, the genotype of low-functioning alleles (A/G + G/G) of the MTR-B12-dependent methionine synthase gene was significantly more frequently determined (in 81.7% of patients – p<0.01).
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