Association of the DNA Methyltransferase and Folate Cycle Enzymes’ Gene Polymorphisms with Coronary Restenosis

Abstract

Background: In recent years, the interest in genetic predisposition studies for coronary artery disease and restenosis has increased. Studies show that polymorphisms of genes encoding folate cycle and homocysteine metabolism enzymes significantly contribute to atherogenesis and endothelial dysfunction. The purpose of this study was to examine some SNPs of genes coding for folate cycle enzymes and DNA methyltransferases as risk factors for in-stent restenosis. Methods: The study included 113 patients after stent implantation and 62 patients without signs of coronary artery disease at coronary angiography as the control group. Real-time PCR and RFLP-PCR were applied to genotype all participants for MTHFR rs1801133, MTHFR rs1801131, MTR rs1805087, MTRR rs1801394, DNMT1 rs8101626, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms. Statistical data processing was carried out using the R language and the SPSS Statistics 20 software. Results: Statistically significant differences in the DNMT3B gene polymorphisms were found between patients with and without in-stent restenosis. An association of TT rs1569686 and TT rs2424913 genotypes with the development of restenosis was revealed. The TT rs1569686 genotype was more frequent in the patients under the age of 65 years and in the subgroup of patients with post-12-month restenosis, as was the minor GG genotype for MTR rs1805087. The homozygous TT genotype for MTHFR rs1801133 was significantly more frequent in the subgroup over 65 years old. The frequencies of the heterozygous genotype for the MTRR gene and the minor GG homozygotes for the DNMT1 gene were significantly higher in the subgroup with in-stent restenosis under 65 years old. Conclusions: The results of this study could be used for a comprehensive risk assessment of ISR development, determining the optimal tactics and an individual approach in the treatment of patients with coronary artery disease before or after percutaneous coronary interventions, including homocysteine-lowering treatment in patients with hyperhomocysteinemia and a high risk of in-stent restenosis.

Effect of hyperhomocysteine in patients after PCI for non-ST-segment elevation myocardial infarction, a retrospective study

“…However, the MTHFR C677T gene has a polymorphism associated with hyperhomocysteinaemia. [32][33][34] In our study protocol, we did not routinely measure serum folate, vitamin B12 and gene polymorphisms, which resulted in no way to understand the interaction between them in terms of risk of cardiovascular events. Third, our sample size was small, which may have led to trial bias.…”

The Significance of Genetically Determined Methylation and Folate Metabolism Disorders in the Pathogenesis of Coronary Artery Disease: A Target for New Therapies?

“…Studies show that polymorphisms in genes encoding the folate cycle significantly contribute to atherogenesis and endothelial dysfunction [51]. For instance, in a me-ta-analysis conducted on over 87,000 participants it was found that the T allele of the 665C>T MTHFR polymorphism is a risk factor for CAD, which is partially mediated by abnormal lipid levels [52].…”

Polymorphic substitutions in folate cycle genes as predictors of hyperhomocysteinemia in children

“…Фолатный цикл как биохимический каскадный процесс превращения ФК в доступное для усваивания организмом производное -5-метилтетрагидрофолат -кон-тролируется MTHFR [11,12]. Вместе с тем обмен фолатов является источником одноуглеродных фрагментов (метильной группы -СН 3 ) для жизненно важных клеточных процессов: биосинтеза пуриновых нуклеотидов и превращения уридинмонофосфата в тимидилат; метилирования ДНК и РНК [13,14]. С помощью ферментов фолатного цикла клеточный яд -ГЦ -переходит в метионин [15,16].…”