The influence of polymorphic variants of folate metabolism genes on homocysteine levels in patients with acute cerebrovascular accident

Disturbances in folate metabolism play a key role in the regulation of homocysteine (Hcy) levels, a sulfur-containing amino acid whose high levels (hyperhomocysteinemia, HHC) are considered an independent risk factor for vascular events, including acute cerebrovascular accident (ACVA). Polymorphisms in genes encoding key enzymes of the folate cycle (MTHFR, MTR, MTRR) can lead to decreased activity and impaired Hcy metabolism. The purpose of the study was to evaluate the effect of allelic variants of folate metabolism genes on homocysteine levels in patients with ACVA. Materials and methods. The prospective study included 69 patients (32 men, 37 women) aged 20 to 98 years (Me = 60 [41; 76]) hospitalized in the neurology department of the regional vascular center with a diagnosis of acute cerebrovascular accident (I63, G45). The genotype of MTHFR C677T (rs1801133) and A1298C (rs1801131), MTR A2756G (rs1805087), MTRR A66G (rs1801394) was determined using Real-Time PCR, and the concentration of Hcy in the serum was determined using the electrochemiluminescence method. Results. The frequency of the unfavorable G allele of the MTRR A66G gene in patients with stroke was 59.56%, which is significantly higher than in the global (51.51%, p=0.013) and European (54.4%, p=0.014) populations according to the NCBI database. Elevated Hcy levels (≥13.4 μmol/L) were detected in 62.32% of patients. A statistically significant association between the G allele of the MTRR gene and the development of HHC was established (p=0.036). No such association was found for the studied polymorphism of the MTHFR and MTR genes. There is also a tendency for the prevalence of HHC to increase with the accumulation of unfavorable alleles of the folate cycle. Conclusion. The obtained data indicate a probable role of the MTRR A66G polymorphism in the development of HHC in patients with stroke. However, ACVA is a multifactorial disease, and only the combined influence of environmental factors, lifestyle, phenotype, and genotype can lead to the development of clinical manifestations.