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

Hyperhomocysteinemia has been identified as a risk factor for venous and arterial thrombosis especially in adult populations. Twenty-eight patients with an initial diagnosis of ischemic stroke and 100 controls, aged <or=18 years, were enrolled in this study. The mean plasma total homocysteine (tHcy) levels in patients and controls were significantly different with values of 8.7+/-3.6 and 7.5+/-2.4 micromol/L, respectively (P=0.01). The plasma tHcy at the 95th percentile was 11.5 micromol/L and patients whose plasma tHcy was above the 95th percentile had an odds ratio of 8.2 (95% confidence interval 1.4-47.2, P=0.02) for developing ischemic stroke. The genetic and acquired factors that could have affected plasma tHcy levels were studied and no differences were found between patients and controls. Factors that were investigated were vitamin B12, red blood cell folate, and serum folate levels as well as methylenetetrahydrofolate reductase C677T polymorphism. It is of note, however, that subjects whose plasma tHcy was above the 95th percentile had significantly lower serum folate levels (P=0.02).
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PMID:Homocysteine, MTHFR C677 T, vitamin B12, and folate levels in Thai children with ischemic stroke: a case-control study. 1716 49

Stroke is a heterogeneous multifactorial disease and is thought to have a polygenic basis. Case-control studies on gene sequence variations have identified a number of potential genetic predisposition factors, but due to the conflicting results, uncertainty remains on the effect of these polymorphisms on risk for the development of stroke. To qualitatively and quantitatively assess the risk associated with different gene polymorphisms for stroke in Asian populations, we comprehensively searched and identified all the studies of association. Clinically overt case-control studies were selected only if neuroimaging had been used as the confirmatory measure for diagnosis of stroke. We performed a meta-analysis of the three most investigated genes, viz., methylenetetrahydrofolate reductase (MTHFR), apolipoprotein E (ApoE) and angiotensin-converting enzyme (ACE). Statistically significant association with stroke were identified for C677T polymorphism of MTHFR [random effects odds ratio (OR) = 1.47, 95% confidence interval (95% CI) 1.19, 1.82; P = 0.0004] and marginally significant association was detected with allele epsilon 4 of ApoE (random effects OR = 1.47, 95% CI 1.00, 2.15; P = 0.049). The sensitivity analysis (exclusion of studies with controls not in Hardy-Weinberg equilibrium) revealed a significant association of stroke with the MTHFR C677T and ApoE epsilon 4 alleles but showed no association with ACE gene insertion/deletion polymorphism.
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PMID:Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis. 1717 Dec 28

Homocysteine is a thiol aminoacid synthesized during the metabolism of methionine. Increased plasma levels of homocysteine can be the result of mutations in the enzymes responsible for homocysteine metabolism, particularly cystathionine-beta synthase (CBS) and 5,10-methylenetetrahydrofolate reductase (MTHFR). Additionally, nutritional deficiencies in B vitamin cofactors required for homocysteine metabolism, including folic acid, vitamin B6 (pyridoxal phosphate), and/or vitamin B12 (methylcobalamin), can induce hyperhomocysteinemia. Over the last decade, following in vitro and in vivo observations of a homocysteine-associated vascular pathology, convincing epidemiological evidence has been gathered on the relation between moderate elevation of plasma homocysteine and vascular disease, including cerebral ischemia. However, causality has yet to be established. The association between homocysteine and ischemic stroke might be a spurious epidemiological finding because of confounding or it might reflect reverse causality. If this is the case, elevated levels of plasma homocysteine should be interpreted as an epiphenomenon secondary to the vascular disease itself. Thus, whether lowering homocysteine concentration prevents cerebral ischemia remains to be determined. The only method to answer the question of the causal relation between homocysteine and ischemic stroke is by intervention trials in which patients at high vascular risk, such as those who have had a recent cerebral ischemic event are randomly allocated to placebo or homocysteine-lowering multivitamin therapy, and followed prospectively. Some of these randomized controlled trials are currently ongoing. Their results should hopefully resolve the issue in the next future.
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PMID:Homocysteine and cerebral ischemia: pathogenic and therapeutical implications. 1730 30

There is evidence to suggest that increased levels of homocysteine play a significant role in vascular disease. It has been suggested that lowering homocysteine levels by dietary folate supplementation may reduce the risk of stroke and coronary heart disease. It is plausible that homocysteine may also play a role in the pathogenesis of abdominal aortic aneurysms (AAA) and that patients with this disease may benefit from folate supplementation. Our objective was to review the published work with regard to the role of homocysteine in the pathogenesis of AAA. Searches were carried out in published work in English with the keywords 'abdominal aortic aneurysm' and 'homocysteine'. There is evidence from in vitro and animal model studies that activation of metalloproteinases by homocysteine can influence aortic wall structure. Several case-control studies report an association between increased levels of homocysteine and the presence of an AAA. There are conflicting genotypic data concerning the association between methylenetetrahydrofolate reductase gene variants and AAA. Although there is evidence for an association between homocysteine and AAA, it is not strong enough to conclude that it plays a causal role in the pathogenesis of AAA. Further research is needed, given the potential benefit that simple vitamin supplementation may have for patients with AAA.
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PMID:Homocysteine and abdominal aortic aneurysms. 1749 68

Stroke is a polygenic or multifactorial disease, and each single susceptibility gene has modest effects. We hypothesize that combined effects of multiple genes might confer a higher stroke risk than a single susceptibility gene. To test our hypothesis we initially recruited 2000 stroke patients (44.3% thrombosis, 28.3% lacunar infarction and 27.4% intracerebral hemorrhage) and 2000 controls, and examined 6 polymorphisms in 5 candidate genes for stroke. Plasma lipoprotein(a) [Lp(a)] level was defined as a categorical variable and also included. Interactions between genetic risk factors were detected by the multifactor dimensionality reduction (MDR) method and further evaluated by multivariate logistic regression analyses. A significant combined effect on stroke due to the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR), the T2354A polymorphism of 5-lipoxygenase activating protein (ALOX5AP), and Lp(a) level, was detected using the MDR method. Furthermore, the combination of MTHFR 677TT, ALOX5AP 2354AA and Lp(a) elevation (Lp(a) concentration > or = 30 mg/dL) was found to be strongly associated with thrombotic stroke in males (OR, 10.419; 95%CI, 2.602 to 41.749; P= 0.001) using the multivariate logistic regression model. In conclusion, our results show that a combination of genetic risk factors can confer a higher risk for stroke than a single risk factor, indicating that people with multiple genetic risk factors have a higher risk of stroke and should be targets for prevention of this disease.
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PMID:Interaction of genetic risk factors confers higher risk for thrombotic stroke in male Chinese: a multicenter case-control study. 1752 9

A 13-year-old Greek girl with pyruvate kinase deficiency and moya moya angiographic pattern is reported. She also had raised serum lipoprotein (a) concentration and was homozygous for the C677T mutation of the methylenetetrahydrofolate reductase gene. She presented with neonatal onset of anemia, hemolytic and aplastic crises, especially during infections, stroke, and also progressive motor and mental deterioration. A digital cranial angiography at 13 years revealed the typical angiographic findings of moya moya angiopathy. This is likely the first patient with pyruvate kinase deficiency and moya moya syndrome and also the combination of elevated serum lipoprotein (a) concentration and the C677T mutation of the methylenetetrahydrofolate reductase gene to be reported. In patients with pyruvate kinase deficiency and moya moya syndrome, a search for raised serum lipoprotein (a) concentrations and the C677T mutation of the methylenetetrahydrofolate reductase gene should be considered.
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PMID:Moya moya syndrome in a child with pyruvate kinase deficiency and combined prothrombotic factors. 1762 33

The authors describe 2 female cousins with neonatal stroke. One was heterozygous for the plasminogen activator inhibitor-1 4G variant and compound heterozygous for the A1298C and C677T methylenetetrahydrofolate reductase mutations. Her cousin was homozygous for the plasminogen activator inhibitor-1 4G variant and heterozygous for the methylenetetrahydrofolate reductase A1298C and factor V Leiden mutations.
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PMID:Two cousins with neonatal stroke, PAI-1 4G variant and MTHFR A1298C mutation. 1764 Dec 64

Previous studies have suggested that both angiotensin II type-1 receptor (AT1R) 1166C and methylenetetrahydrofolate reductase (MTHFR) 677T variants can have disadvantageous effects on the small-vessel circulation under certain conditions. The purpose of this study was to analyze the possible consequences of the simultaneous distribution of these two genetic variants in different types of ischemic stroke. The genetic and clinical data on 357 ischemic stroke patients and 263 control subjects were analyzed by using univariate and logistic statistical approaches. Neither the MTHFR 677T nor the AT1R 1166C genetic variant alone conferred the risk of any subtype of ischemic stroke. The combination of the homozygous MTHFR 677TT genotype and at least one AT1R 1166C allele occurred more frequently in the ischemic stroke patients (8.68%) than in the controls (4.56%, p < 0.05). Specific subclassification of the patients revealed an accumulation of this combination in small-vessel-associated ischemic stroke (12.2%, p < 0.01); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.66 (95% confidence interval, 1.28-7.89; p < 0.05). These findings suggest that the combination of these two genetic factors can contribute to the development of small-vessel cerebral infarcts. Although the exact mechanism of action is not known, addition of the unfavourable effects on the endothelial function can be presumed.
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PMID:The combination of homozygous MTHFR 677T and angiotensin II type-1 receptor 1166C variants confers the risk of small-vessel-associated ischemic stroke. 1772 26

Plasma homocysteine (Hcy) concentration has been shown to be influenced by a mutation in the gene coding methylenetetrahydrofolate reductase (MTHFR). Although plasma Hcy has been shown to be related to atherosclerotic disorders, the association between MTHFR gene polymorphism and ischemic stroke remains controversial. In the present study we investigated the association between MTHFR gene polymorphism and risk factor-dependent augmentation for ischemic stroke in subjects with several risk factors for atherosclerosis, with special emphasis on the risk factor-gene interaction. The diagnosis of cerebral infarction in each patient was confirmed by computed tomography (CT) findings of the brain. MTHFR C677T polymorphism was genotyped with a conventional method. In 97 stroke patients (48 cases of atherothrombotic infarction, 38 cases of lacunar infarction, 9 cases of cardiac embolism, 2 others) and 241 age-and sex-matched healthy control subjects, the frequencies of the T allele were 0.44 and 0.39, respectively. In patients with CT-proven atherothrombotic infarction, the T allele frequency was 0.54 (P = .033 vs controls). The adjusted odds ratio in subjects with TT genotype for atherothrombotic infarction was 3.87 (95% confidence interval = 1.27-11.8). A general linear model analysis showed that an interaction between the HDL-C and MTHFR genotype was significantly associated with atherothrombotic infarction (F = 5.695; P = .018). These findings indicate that the T allele of the MTHFR gene is significantly associated with atherothrombotic infarction. Furthermore, the analysis of risk factor-gene interaction could be a useful tool for deriving specific predictive information about ischemic stroke in an elderly Japanese population.
J Stroke Cerebrovasc Dis
PMID:An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and ischemic stroke. 1790 3

The aim of this study was to evaluate the prevalence of factor V Leiden (FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations, and angiotensin-converting enzyme (ACE) I/D polymorphism in ischemic stroke (IS) patients. A total of 162 Turkish IS patients were included and analyzed according to stroke subtype by the TOAST classification. Their genotype data were compared with those of the control group, representing the healthy population, using the chi(2) test. The frequency of FVL heterozygocity was 12.3% in this series-higher than that in the normal population (9.8%; statistically insignificant, P = .478). The frequency of the ACE D/D genotype in all stroke patients and those with stroke of undetermined etiology was higher than that in our population (52.5% and 59.2%, respectively, vs 39.3%; statistically significant, P = .034, P = .020). Our results may suggest that ACE D/D genotype is a risk factor for IS, particularly in those with stroke of undetermined etiology in the Turkish population.
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PMID:Prevalence of thrombophilic mutations and ACE I/D polymorphism in Turkish ischemic stroke patients. 1838 82


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