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)

It was the aim of this study to determine the associations of clinical and laboratory data with plasma homocyst(e)ine levels in patients with transient ischemic attack (TIA) or minor stroke (MS), with special reference to their 677C to T mutation status in the 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene. Seventy-six patients with TIA or MS were investigated at least 3 months after their (last) clinical event. By means of univariate analysis, significant correlations of homocyst(e)ine levels with male gender (P<0.02), age (P<0.0005), creatinine levels (P<0.0002), folate levels (inversely, P<0.05), and alcohol use (P<0.02) were found, but not with vitamin B12 levels. Multivariate regression analysis, including age, creatinine levels, and folate levels as independent variables, revealed age (P<0.01) and creatinine levels (P<0.02) to be significantly correlated with homocyst(e)ine levels. After adjustment for age, creatinine levels and homocyst(e)ine levels remained significantly correlated to each other (P<0.005), whereas the relation between folate levels and homocyst(e)ine levels was no longer significant (P=0.10). Mutation-positive patients exhibited moderately and statistically non-significantly higher homocyst(e)ine levels than mutation-negative patients, particularly those who were homozygous positive. Homocyst(e)ine levels were closely correlated with creatinine levels (P<0.0002) and with folate levels (inversely, P<0.05), but only in mutation-positive and not in mutation-negative patients. Homozygous positive, heterozygous positive, and mutation-negative patients did not differ with respect to clinical and laboratory data concerning 'risk factors for stroke' or co-existing vascular disease. In conclusion, the associations of creatinine levels and, inversely, of folate levels with plasma homocyst(e)ine levels in patients with TIA or MS are dependent on the 5,10-MTHFR mutation status. Significant correlations between these variables were found only in mutation-positive but not in mutation-negative patients.
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PMID:677C to T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and plasma homocyst(e)ine levels in patients with TIA or minor stroke. 956 60

A common C677T mutation in the gene for the enzyme 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) has been linked to elevated levels of homocysteine and was therefore suspected to be a candidate genetic risk factor for arterial occlusive disease. Another mutation, factor V Leiden, has been established as a common hereditary risk factor for venous thrombosis, but its role in arterial disease remains controversial. We investigated the prevalence of both the C677T MTHFR mutation and the factor V Leiden mutation in 81 patients with transient ischemic attack (TIA) or minor stroke (MS) and in 81 age- and sex-matched control subjects free from clinically manifest vascular disease. We further compared clinical and laboratory data as well as clinical course of patients carrying the factor V Leiden mutation alone or in combination with the C677T MTHFR mutation and mutation-free patients. The prevalence of the MTHFR mutation did not differ between patients and control subjects with 11.1% homozygous carriers in both groups (OR for homozygous carriers 1.0; 95% CI 0.38-2.66). However, there was a trend towards a higher prevalence of carriers of factor V Leiden in patients (12.3%) than in control subjects (4.9%) (OR 2.75; 95% CI 0.83-9.17;p=0.09). Furthermore, we found some evidence that the combined occurrence of the C677T MTHFR mutation and factor V Leiden might unfavorably affect the clinical course of the disease, but the number of respective patients was small. Larger studies with a greater number of carriers of both the C677T MTHFR mutation and factor V Leiden seem therefore warranted.
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PMID:C677T MTHFR mutation and factor V Leiden mutation in patients with TIA/minor stroke: a case-control study. 995 Feb 59

Mild hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. Homozygosity for the C677T mutation in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) is frequently associated with hyperhomocysteinemia, particularly in individuals with low levels of serum folate, and has been directly associated with cardiovascular disease in certain populations. The purpose of this study was to establish whether the C677T mutation, which causes thermolabile MTHFR, is a risk factor for ischemic stroke in the Irish population. The homozygous C677T genotype has previously been associated with coronary heart disease in Ireland. We collected blood from 174 individuals (minimum age 60 years) who had suffered an ischemic stroke that was confirmed by computed tomography brain scan. Control subjects (n=183) aged >/=60 years, who had never suffered a stroke or transient ischemic attack, were recruited from hospitals and active retirement groups in the same geographical area. MTHFR genotypes were determined and other known risk factors for stroke were documented. In the control group, the frequency of subjects with the homozygous C677T genotype was 10.4%. In patients who had suffered ischemic stroke, the frequency was 15.5%. This difference was not statistically significant. The odds ratio of stroke for C677T homozygotes, with other genotypes as a reference group, was 1.59, 95% CI=0.85, 2.97. The data indicate that the homozygous C677T MTHFR genotype is at most a moderate risk factor for ischemic stroke.
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PMID:Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke. 997 99

Moderately elevated plasma homocysteine levels have been established as an independent risk factor for atherosclerosis and its complications, including cerebrovascular disease. A common mutation (C677T) in the gene encoding for the enzyme methylenetetrahydrofolate reductase (MTHFR) has been linked to increased plasma homocysteine levels in homozygous carriers, particularly in the presence of low folate levels. However, the results of most of the previous studies suggest that the C677T MTHFR mutation is not a significant risk factor for arterial disease. This discrepancy might, at least partly, be due to the fact that plasma homocysteine levels are influenced by several other factors, including age, gender, renal function, and vitamin status. We investigated the relation between plasma homocysteine levels, the C677T MTHFR mutation, and these other factors in a population of 96 patients with transient ischemic attacks or minor strokes and in 96 age- and sex-matched healthy control subjects. We further tested the value of a multivariate model for the prediction of plasma homocysteine levels under particular consideration of the MTHFR mutation status. In the patients, plasma homocysteine levels were significantly higher than in the healthy control subjects. With regard to the MTHFR mutation, the distribution of the C/C, C/T, and T/T genotypes was not significantly different between patients and healthy control subjects. Univariate (linear regression) analysis revealed significant (positive) correlations between plasma homocysteine levels on the one hand and age and creatinine on the other, the latter particularly in subjects with creatinine levels in the upper quartile. Significant (negative) correlations were found between plasma homocysteine levels, vitamin B12, and folate levels. However, these relations could much better be expressed by means of a multiplicative regression model. T/T subjects exhibited slightly higher homocysteine levels than C/C and C/T subjects; however, the differences between the 3 genotypes were not significant. Multivariate (stepwise regression) analysis revealed age, vitamin B12 levels, folate levels, and creatinine levels as significant independent variables influencing plasma homocysteine levels, whereas the MTHFR mutation status and gender were removed from the model. Considering all 192 subjects, only 28.8% of the variance of plasma homocysteine levels could be accounted for by the model. However, in homozygous carriers of the MTHFR mutation, the predictive power of the model is very high, explaining 76.1% of the variance of plasma homocysteine levels. According to our results, the C677T mutation does not constitute a major risk factor for transient ischemic attack or minor stroke, even under consideration of other possibly confounding factors that are known to affect plasma homocysteine levels. However, it is possible to predict plasma homocysteine levels in homozygous carriers of the mutation with high accuracy. The knowledge of the MTHFR mutation status may therefore help to identify subjects at high risk for hyperhomocysteinemia.
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PMID:Genetic and nongenetic factors influencing plasma homocysteine levels in patients with ischemic cerebrovascular disease and in healthy control subjects. 1036 Jun 32

A common mutation in methylenetetrahydrofolate reductase (MTHFR), a homocysteine metabolic pathway enzyme, has been associated with increased homocysteine levels and increased risk for premature cardiovascular disease. The purpose of this study was to assess the association between the prevalence of the MTHFR mutation, hyperhomocysteinemia, and subtypes of ischemic stroke in an elderly population comprised of three age-balanced groups of patients. The presence of the C677T MTHFR mutation was determined by a direct polymerase chain reaction-based assay performed on blood samples from 136 patients with acute ischemic stroke, 95 patients with atherosclerotic risk factors for stroke (including some with a history of previous stroke or transient ischemic attack), and 52 healthy control subjects. The prevalence of the homozygous C677T mutation was not significantly higher in the elderly stroke patients (7%) than in the atherosclerotic risk (8%) or healthy elderly control (2%) groups. Plasma homocysteine levels were higher in the acute stroke patient group (14.5+/-4.5 micromol/L) and atherosclerotic risk patient group (14.6+/-6.2 micromol/L) compared with the control subjects (10.3+/-3.1 micromol/ L, P < 0.03). Homozygotes for the C677T MTHFR mutation did not have significantly higher homocysteine levels than non-homozygotes. Moderate hyperhomocysteinemia, though common in older patients with ischemic cerebrovascular disease, is not attributable, at least in this patient group, to a higher prevalence of the C677T MTHFR mutation.
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PMID:Role of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase in ischemic stroke. 1040 94

In this study of 118 children (median age 5.1 years; range 6 months to 17 years) with ischaemic stroke or transient ischaemic attack (TIA), 22 children (19%) were homozygous for the thermolabile variant of the methylenetetrahydrofolate reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular disease (CVD), 17 of 84 were homozygous for the t-MTHFR allele (p=0.13 compared with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a significant (p<0.025) increment of plasma total homocysteine concentration in homozygotes for the t-MTHFR allele compared with heterozygotes, negatives for the t-MTHFR allele, and control children with no history of stroke. In four of 12 homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised, compared with three of 38 of those who were negative or heterozygous (p=0.047; OR 5.8, 95% CI 1.1 to 31.2). Homozygotes for the t-MTHFR allele were significantly more likely to have a recurrent event than those who were negative or heterozygous (Cox regression p=0.031, hazard ratio 2.18, 95% CI 1.08 to 4.42). These data suggest that homozygosity for the t-MTHFR allele is associated with raised homocysteine levels in children and is a risk factor for primary and secondary stroke and TIA.
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PMID:Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood. 1130 98

Twin and family-based studies indicate that genetic factors might be involved in the risk of transient ischemic attack (TIA) and ischemic stroke (IS). Identification of genetic risk factors for new vascular events after cerebral ischemia may target secondary prevention. The overall aim of POLARIS is to study which polymorphisms predispose to new vascular events after TIA/IS and to assess their predictive value. Patients who have had a TIA or IS of presumed arterial origin are included. The study design is twofold. In part one the prevalences of polymorphisms will be compared between 300 long-term survivors of the Dutch TIA Trial (average follow-up 10 years) and 820 patients with recent TIA/IS. In part two a cohort of 820 patients with recent TIA/IS will be followed for the occurrence of vascular events for an average of 3.5 years. Several polymorphisms of interest will be genotyped, including factor V Leiden, prothrombin 20210A, 5,10-methylenetetrahydrofolate reductase, HR2 haplotype factor V and factor XIII Val34Leu.
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PMID:Polymorphisms and Risk of Ischemic Stroke (POLARIS) study: rationale and design. 1463 Nov 27

Cervical-artery dissection (CAD) is a major cause of cerebral ischaemia in young adults and can lead to various clinical symptoms, some of which are benign (eg, headache, neck pain, Horner's syndrome, and cranial-nerve palsy), but most patients have a stroke or transient ischaemic attack. In addition to trauma to the neck, other risk factors have been suggested, such as infection, migraine, hyperhomocysteinaemia, and the 677TT genotype of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR 677TT), although evidence is sparse. An underlying arteriopathy, which could in part be genetically determined, is believed to have a role in the development of CAD. Importantly, both research on and optimum management of CAD strongly rely on diagnostic accuracy. Although the functional outcome of CAD is good in most patients, socioprofessional effects can be important. Incidence of the disorder in the general population is underestimated. Mortality and short-term recurrence rates are low but possibly also underestimated. Further research is warranted to improve our understanding of the underlying pathophysiology, to assess the long-term outcome, and ultimately to provide treatment and prevention strategies.
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PMID:Cervical-artery dissections: predisposing factors, diagnosis, and outcome. 1953 38