Methylation is a biochemical process involving the addition of a methyl group (-CH₃) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels, and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folate (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Background: Single nucleotide polymorphisms in gene encoding is the key enzyme in the folates pathway, methyltetrahydrofolate reductase (MTHFR), which causes methylation disorders associated with coronary artery disease (CAD). We evaluated associations between methylation disorders caused by MTHFR gene polymorphisms and the blood folate concentrations (folic acid, 5-MTHF) in CAD patients. Methods: Study group: 34 patients with CAD confirmed by invasive coronary angiography (ICA). Controls: 14 patients without CAD symptoms or significant coronary artery stenosis, based on ICA or multislice computed tomography (MSCT) with coronary artery calcification (CAC) scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined using Liquid Chromatography-Mass Spectrometry (LC-MS). Results: The c.[1286A>C];[1286A>C] MTHFR polymorphism occurred significantly more often in (CAD⁺) patients compared to the (CAD⁻) cohort and to the selected general European “CEU_GENO_PANEL” population sample. The concentration of 5-MTHF and folic acid in subgroups of CAD⁺ patients with methylation disorders categorized by genotypes and CAD presence (CAD⁺) was always lower in CAD⁺ subgroups compared to non-CAD individuals (CAD⁻). Conclusions: Further studies on a larger scale are needed to implicate the homozygous c.1286A>C MTHFR variant as CAD genetic marker and the 5-MTHF as CAD biomarker. Identification of high CAD risk using genetic and phenotypic tests can contribute to personalized therapy using an active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymorphisms.

Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Background: The presence of single nucleotide polymorphisms in the gene encoding key en-zyme in the folate pathway methyltetrahydrofolate reductase (MTHFR), causes methylation disorders associated with CAD development. Methods: Study group: 42 patients with CAD con-firmed by coronary angiography. Controls: 16 patients without CAD symptoms or significant coronary artery stenosis, based on invasive coronary angiography or multislice computed to-mography with coronary artery calcification scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined by LC-MS. Results: c.[1286A>C];[1286A>C] MTHFR polymorphism occurred significantly more often in (CAD+) patients compared to (CAD-) cohort and to the European population. The con-centration of 5-MTHF and folic acid in the subgroups of patients with methylation disorders di-vided by genotypes and (CAD+) was lower compared to (CAD-). Conclusions: The homozygous c.1286 A>C MTHFR variant can be considered as CAD genetic marker. In the subjects with the c.1286 A>C heterozygous and homozygous genotypes, lower concentrations of methyltetrahy-drofolate (5-MTHF) were observed. 5-MTHF can be considered as a biomarker of CAD. Identifi-cation of people at high risk of CAD using genetic tests can contribute to personalized therapy using active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymor-phisms.