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)

Plasma homocysteine levels depend in part on the molecular nature of the methylenetetrahydrofolate reductase (MTHFR) and on blood folate intake. Little has been reported on platelet counts in the presence of hyperhomocysteinemia and MTHFR polymorphisms, with the exception of delayed platelet recovery in homozygous MTHFR C677T subjects after treatment with methotrexate for ovarian cancer. The aim of this investigation was to evaluate the possibility of a link between the platelet count and plasma homocysteine levels in different MTHFR variants in 165 female patients. Determinations of plasma homocysteine levels were by ELISA and of MTHFR polymorphisms (A1298C and C677T) were by inverse hybridization. Serum P- and E-selectin concentrations were obtained by ELISA. An inverse correlation (R=-0.88, P<0.001) was observed between blood platelet counts and plasma homocysteine levels in the women homozygous for MTHFR C677T. This correlation did not depend on pregnancy or other variables reported. Serum concentrations of sE- and sP-selectin, markers of endothelial and platelet activation, were significantly and positively correlated with homocysteine levels. These findings suggest that homocysteine affects platelet numbers in women with MTHFR C677T possibly consequent to endothelial and platelet activation.
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PMID:Homocysteinemia is inversely correlated with platelet count and directly correlated with sE- and sP-selectin levels in females homozygous for C677T methylenetetrahydrofolate reductase. 1601 63

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.
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PMID:[Role of the polymorphisms within genes encoding proteins related to endothelial dysfunction in coronary artery disease]. 2253 55