Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated plasma homocysteine concentrations are associated with an increased risk of cardiovascular disease, but the relationship has not been proven to be causal. Folate is the strongest nutritional and pharmacological determinant of plasma homocysteine concentrations, which also interact with the genetic variation in methylenetetrahydrofolate reductase (MTHFR). Endothelial dysfunction due to reduced nitric oxide bioavailability is an early feature of vascular pathology. This can be assessed noninvasively by measurement of flow-mediated dilatation. Human studies on folic acid, homocysteine and endothelial function are reported. It is proposed that folic acid in high doses may have beneficial effects on endothelial function, which are independent of homocysteine lowering.
 ...
PMID:Folate, homocysteine, endothelial function and cardiovascular disease. What is the link? 1168 75

Cardiovascular disease has a multifactorial aetiology that is influenced by both genetic and environmental factors. Endothelial dysfunction is a key event in the pathogenesis of vascular disease that occurs before structural vascular changes or clinical symptoms are evident. Conventional risk factors, for example hypertension and diabetes mellitus, are associated with endothelial dysfunction, but the influence of other putative risk factors is not clear. The methylenetetrahydrofolate reductase (MTHFR) C677T genotype, a common polymorphism that induces hyperhomocysteinaemia, has been proposed as being a genetic risk factor for cardiovascular disease. A total of 126 healthy adults recruited by MTHFR C677T genotype (42 of each genotype, i.e. CC, CT and TT) underwent assessment of endothelial function. Brachial artery endothelium-dependent flow-mediated dilatation (FMD) was measured using high-resolution ultrasonic vessel "wall-tracking". Using multiple regression analysis, MTHFR genotype and 21 other subject and subject-lifestyle variables were investigated as potential predictors of endothelial function. FMD was influenced positively by frequency of aerobic exercise and by hormone replacement therapy, and negatively by increases in systolic blood pressure. MTHFR C677T genotype and the associated variation in plasma homocysteine levels did not influence FMD. Additionally, other factors, including plasma cholesterol and self-supplementation with either antioxidant vitamins or cod liver oil, showed no significant relationship with FMD, although these findings are compromised by the narrow range studied for cholesterol and the small number of subjects taking supplements. These observations have implications for risk factor management in the primary prevention of cardiovascular disease in healthy individuals.
 ...
PMID:Influence of methylenetetrahydrofolate reductase genotype, exercise and other risk factors on endothelial function in healthy individuals. 1174 60

Endothelial dysfunction is crucial in the development of atherosclerotic lesions. There is number of factors involved in this process, e.g. hypercholesterolemia, hyperhomocysteinemia, free radicals, hypertension, obesity or overweight, smoking. Polymorphisms of the genes encoding products involved in the atherosclerotic process play significant role in the etiology of atherosclerosis and coronary artery disease (CAD). The aim of the present study was to show the role of the factors and markers of endothelial dysfunction e.g. methylenetetrahydrofolate reductase (MTHFR), E-selectin (CD62E) and intercellular adhesion molecule-1 (ICAM-1) and common polymorphisms within genes encoding these molecules in the etiology of CAD. MTHFR catalyzes a reduction of 5,10-methylenetetrahydrofolate to 5-methyletetrahydrofolate that is the carbon donor for the remethylation ofhomocysteine (Hcys) to methionine. The 677C>T polymorphism in the MTHFR gene influences enzyme thermolability that leads to its decreased activity and in consequence to elevated level of plasma Hcys. E-selectin is synthesized by the endothelium after the activation of inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). The C allele of the 561A>C polymorphism within CD62E is suggested to be a risk factor for restenosis in CAD patients. Another polymorphism in CD62E gene, 98G>T polymorphism is suggested to be a marker of the 561A>C polymorphism and both of these changes are likely to control the E-selectin expression. The 1405A>G polymorphism in ICAM1 gene may affect mRNA splicing patterns that modify cell-cell interactions and influence inflammatory response.
 ...
PMID:[Role of the polymorphisms within genes encoding proteins related to endothelial dysfunction in coronary artery disease]. 2253 55