ANALYSIS OF RELATIONSHIP BETWEEN POLYMORPHISM OF MTHFR (C677T), MTHFR (A1298C), MTR (A2756G) GENES IN THE DEVELOPMENT OF ISCHEMIC STROKE IN YOUNG PATIENTS.

Abstract

The study focuses on investigation of the role of polymorphic variants of MTHFR (C677T), MTHFR (A1298C), MTR (A2756G) folate metabolism genes and their combinations in the development of ischemic stroke in young people. The study included 2 groups of patients: 61 young patients aged 18 - 44 years old with acute ischemic stroke (main group) and 29 middle-age patients, 45 to 59 years old with ischemic stroke (control group). To analyze polymorphic DNA loci, the standardized test systems TagMan Mutation Detection Assays Lifa-Technology (USA) were used. MTHFR C677T (rs 1801133), MTHFR A1298C (rs 1801131), and MTR A2756G (rs1805087) polymorphisms were involved. Polymorphic variants of MTHFR (C677T), MTHF (A1298C), MTR (A2756G) genes were analyzed, using the polymerase chain reaction (PCR) method. The study of homocysteine level ​​in blood plasma was carried out, using the method of enzyme-linked immunosorbent analysis. The patients of the main group with the homozygous variant G/G showed a statistically significant high level of homocysteine ​- 18.9±4.8 ng/ml compared with patients with the A/A genotype - 12.4±4.2 ng/ml and A/G - 12.9±4.8 ng/ml, (p=0.045). The main group showed an increased risk of ischemic stroke associated with 677CT (OR=2.39; CI=1.12-5.06) and 677TT genotypes (OR=4.45; CI=1.08-25.44) for the MTHFR gene. When carrying out a comparative analysis of the А1298С polymorphism of the MTHFR gene, 1298CC genotype (OR=1.45; CI=0.46-3.99) and 1298AC genotype (OR=2.4; CI=1.6-5.9) were statistically significant. Comparative analysis of А2756G polymorphism of the МТR gene showed that the GG genotype was statistically significant (OR=2.68; CI=1.10-7.069). An increase in the development of ischemic brain lesions was associated with polymorphic variants of CT for the MTHFR gene, AC for the MTHFR gene, and GG for the MTR gene. An increase in the risk of developing ischemic brain lesions was associated with polymorphic variants of CT + TT (CI=1.8-10.9) for the MTHFR gene, AC + CC (CI=1.31-6.32) for the MTHFR gene, AG + GG (CI=1.57-10.08) for the MTR gene. The study shows that in young people homozygote for minor alleles C/C for A1298C of the MTHFR gene polymorphism and T/T for C677T of the MTHFR gene and G/G for A2756G of the MTR gene polymorphism increases the risk of ischemic stroke, compared with carriers of A/A for A1298C, C/C for C677T of the MTHFR gene and А/А by А2756G of the МТR gene.