The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a process essential for the methylation of homocysteine to methionine. Polymorphisms in the MTHFR gene can reduce enzyme activity, disrupting the folate cycle and leading to hyperhomocysteinemia. The two most common polymorphisms associated with this gene are 667C>T (rs1801133) and 1298A>C (rs1801131). Background: This review provides a comprehensive summary of the current knowledge regarding MTHFR polymorphisms, with a particular focus on their potential impact on disease susceptibility. We hope this review will serve as a valuable resource for understanding the significance of MTHFR polymorphisms and their complex relationships with various diseases. Methods: For this review, we prioritized recent evidence, focusing on reviews and meta-analyses published between 2015 and 2025, sourced from PubMed and Google Scholar. Results: We explore the connection between these polymorphisms and a broad spectrum of medical conditions, including cardiovascular diseases and oxidative stress pathology; neurological and psychiatric disorders, such as Autism Spectrum Disorder, Alzheimer’s disease, Schizophrenia, and Major Depressive Disorder; fertility, pregnancy, and neonatal complications, including recurrent pregnancy loss, pre-eclampsia, preterm birth, low birth weight, and neural tube defects; metabolic disorders, such as diabetes mellitus, inflammatory bowel disease, and non-alcoholic fatty liver disease; and oncological conditions, including breast, prostate, and ovarian cancers; as well as leukemia, and autoimmune diseases, particularly rheumatoid arthritis. Conclusions: While some diseases have a well-established association with MTHFR polymorphisms, others require further investigation. Our analysis highlights the crucial role of environmental factors, such as ethnic background and dietary folate intake, in influencing study outcomes.

The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a process essential for the methylation of homocysteine to methionine. Polymorphisms in the MTHFR gene can reduce enzyme activity, disrupting the folate cycle and leading to hyperhomocysteinemia. The two most common polymorphisms associated with this gene are 667C>T (rs1801133) and 1298A>C (rs1801131). Background: This review provides a comprehensive summary of current knowledge regarding MTHFR polymorphisms, with a particular focus on their potential impact on disease susceptibility. We hope this review will serve as a valuable resource for understanding the significance of MTHFR polymorphisms and their complex relationships with various diseases. Methods: For this review, we prioritized recent evidence, focusing on reviews and meta-analyses published between 2015 and 2025, sourced from PubMed and Google Scholar. Results: We explore the connection between these polymorphisms and a broad spectrum of medical conditions, including: cardiovascular diseases and oxidative stress pathology, neurological and psychiatric disorders, such as Autism Spectrum Disorder, Alzheimer’s disease, Schizophrenia, and Major Depressive Disorder, fertility, pregnancy, and neonatal complications, including recurrent pregnancy loss, preeclampsia, preterm birth, low birth weight, and neural tube defects, metabolic disorders, such as diabetes mellitus, inflammatory bowel disease, and non-alcoholic fatty liver disease, oncological conditions, including breast, prostate, and ovarian cancers, as well as leukemia, autoimmune diseases, particularly rheumatoid arthritis. Conclusions: While some diseases have a well-established association with MTHFR polymorphisms, others require further investigation. Our analysis highlights the crucial role of environmental factors, such as ethnic background and dietary folate intake, in influencing study outcomes.

Background/Objectives: Coronary artery disease (CAD) and aortic stenosis (AS) frequently coexist and share similar pathophysiological pathways, including inflammation, lipid deposition, and extracellular matrix remodeling. Trace elements are involved in cellular and physiological processes, playing regulatory and signaling roles. Their concentrations may be altered in various pathological conditions. The aim of our study was to compare trace metal concentrations in patients with severe aortic stenosis with and without coexisting coronary artery disease. Methods: In 53 patients (25 male, 47.2%, median age of 78 (75–81) years) with severe aortic stenosis, CAD coexistence and progression were analyzed based on the most recent coronary angiography report and history of revascularization. Blood samples for trace element analysis were collected prior to the implantation of the prosthesis, from the peripheral artery and by the pigtail catheter at the aortic root. Results: Twenty-six patients presented any degree of CAD, and were further differentiated into more advanced disease stages. The analysis found that patients with CAD had lower median concentrations of aluminum and calcium in the peripheral blood, and manganese and selenium in the aorta. Furthermore, in most advanced CAD patients, the concentration of magnesium, calcium, nickel, and copper in peripheral blood, along with chromium and selenium in aortic blood, was found to be lower compared to non-CAD patients. Lower selenium in aortic blood samples was predictive of an advanced stage of CAD. Conclusions: Patients with severe aortic stenosis and coexisting CAD present significantly lower blood concentrations of trace elements compared to those with the isolated disease.