1Taras Shevchenko National University of Kyiv, department of Internal Medicine; Ukraine.
2City Clinical Ambulance Hospital, department of Neurosurgery N2, Ukraine.
Georgian Med News. 2021 Oct(319):87-92.
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.
该研究侧重于调查 MTHFR（C677T）、MTHFR（A1298C）、MTR（A2756G）叶酸代谢基因的多态性变体及其组合在年轻人缺血性中风发展中的作用。该研究包括 2 组患者：61 名年龄在 18-44 岁的急性缺血性中风年轻患者（主要组）和 29 名年龄在 45-59 岁的缺血性中风中年患者（对照组）。为了分析多态性 DNA 位点，使用了标准化的 TagMan 突变检测分析系统 Lifa-Technology（美国）。涉及 MTHFR C677T（rs1801133）、MTHFR A1298C（rs1801131）和 MTR A2756G（rs1805087）多态性。使用聚合酶链反应（PCR）方法分析 MTHFR（C677T）、MTHF（A1298C）、MTR（A2756G）基因的多态性变体。使用酶联免疫吸附分析方法检测血浆中同型半胱氨酸水平。与 A/A 基因型（12.4±4.2ng/ml）和 A/G（12.9±4.8ng/ml）相比，主组中同型半胱氨酸水平显著升高的纯合变体 G/G 患者为 18.9±4.8ng/ml（p=0.045）。与 A/A 基因型相比，主组中携带 677CT（OR=2.39；95%CI=1.12-5.06）和 677TT 基因型的患者发生缺血性中风的风险增加（OR=4.45；95%CI=1.08-25.44）。MTHFR 基因。当对 MTHFR 基因的 1298C 多态性进行比较分析时，1298CC 基因型（OR=1.45；95%CI=0.46-3.99）和 1298AC 基因型（OR=2.4；95%CI=1.6-5.9）具有统计学意义。对 MTR 基因的 A2756G 多态性进行比较分析表明，GG 基因型具有统计学意义（OR=2.68；95%CI=1.10-7.069）。携带 MTHFR 基因的 CT 多态性、MTHFR 基因的 AC 多态性和 MTR 基因的 GG 多态性与缺血性脑损伤的发展增加相关。携带 MTHFR 基因的 CT+TT（95%CI=1.8-10.9）、MTHFR 基因的 AC+CC（95%CI=1.31-6.32）和 MTR 基因的 AG+GG（95%CI=1.57-10.08）与缺血性脑损伤的风险增加相关。研究表明，与 A1298C 多态性的 A/A 携带者相比，MTHFR 基因的 A1298C 多态性的 C/C 纯合子和 MTHFR 基因的 C677T 多态性的 T/T 以及 MTR 基因的 A2756G 多态性的 G/G 携带者发生缺血性中风的风险增加。
