Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Thrombophilia by definition represents acquired and/or genetic conditions that predispose patients to both venous and arterial thromboembolic events. Thrombosis is the most common cause of death worldwide. On the arterial side, myocardial infarction and stroke result in significant morbidity and mortality. Venous thromboembolic events most commonly involve the deep veins of the lower extremity with potential complications of pulmonary emboli. Pregnancy is a hypercoagulable state, and thromboembolism is the leading cause of antepartum and postpartum maternal mortality. With the description by Dahlback in 1993 of a condition initially labeled activated protein C resistance, significant advances have rapidly followed. Activated protein C resistance was linked to an underlying point mutation resulting in coagulation factor V (factor V Leiden). Recent attention has focused on certain inherited thrombophilic factors that may predispose to arterial and/or venous thromboses and their possible association with pregnancy complications, including early pregnancy loss. These include a group of mostly autosomal dominant, inherited gene mutations leading to a hypercoagulable state, such as factor V Leiden G1691A, factor II or prothrombin G20210A, and hyperhomocysteinemia associated with methylenetetrahydrofolate reductase C677T mutation. In addition, deficiencies in protein S, protein C, and antithrombin can lead to a hypercoagulable state. Although some studies of recurrent pregnancy loss patients with a positive test for an inherited thrombophilia are conflicting, a case-control study of untreated recurrent miscarriage patients who were heterozygous for the factor V Leiden mutation revealed a lower success rate than the controls who had a history of idiopathic recurrent miscarriage. With the identification of genetic risk factors, there has been synergistic amplification of thrombotic risk when one has an abnormal gene (e.g., factor V Leiden) plus environmental issues (e.g., pregnancy). Current understanding indicates that a combination of risk factors, including multiple inherited thrombophilic defects associated with secondary hypercoagulable states, have a particularly strong association with adverse pregnancy outcome.
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PMID:Thrombophilias and recurrent pregnancy loss. 1641 78

Genetic background plays an important role in susceptibility to ischemic stroke. Our aim was to investigate the association of genetic polymorphisms and ischemic stroke and to evaluate their interaction with environmental risk factors in the Chinese population. Angiotensin-converting enzyme (ACE) gene I/D polymorphism, apolipoprotein E (ApoE) gene polymorphism, methylenetetrahydrofolate reductase (MTHFR) gene 677C/T polymorphism, and beta fibrinogen (Fgbeta) gene 148C/T polymorphism were analyzed in 100 patients and 100 matched controls. The subjects were genotyped by polymerase chain reaction (PCR) amplification and denaturing high-performance liquid chromatography (DHPLC) analysis. Persons with the Fgbeta CT/TT, MTHFR CT/TT, and ACE ID/DD genotypes had an elevated incidence of ischemic stroke (OR 3.907, 95% CI, 1.160-13.162, P=0.028). Smokers with the Fgbeta CT/TT or APOEepsilon4epsilon3 genotype, as well as individuals with the Fgbeta CT/TT genotype who consumed alcohol were more likely to develop a stroke. The data indicate that certain unfavorable genotypic combinations act synergistically in the development of ischemic stroke in the Chinese population. Synergism was also observed between genotype and environmental risk factors. This study may facilitate the development of a strategy to effectively prevent ischemic strokes.
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PMID:Association studies of genetic polymorphism, environmental factors and their interaction in ischemic stroke. 1644 28

The contribution of mutations in the prothrombin (FII G20210A), methylenetetrahydrofolate reductase (C677T) genes and factor V Leiden (FVL) to the pathogenesis of arterial thrombosis remains controversial. In this study, these polymorphisms were investigated by polymerase chain reaction-restriction fragment length polymorphism in a group of 53 patients that presented arterial thrombosis other than myocardial infarction as a first thrombotic event and 275 control subjects living in the state of Minas Gerais, Brazil. Odds ratio (OR) and chi tests were applied for statistical comparisons. Similar frequencies were detected among patients and control subjects for the C677T mutation. The 20210A mutation was present in 3.6% of the control subjects but was not detected among ischemic stroke patients. Significant differences were detected only for factor V Leiden (odds ratio 7.11; 95% confidence interval 1.55-32.73). Our data indicate that, among these genetic factors, factor V Leiden was identified as an important risk factor for arterial thrombosis in this group of patients. In addition, our results indicate regional differences in the incidence of these genetic factors in Brazil, as compared to the incidences reported in other studies.
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PMID:Factor V Leiden and increased risk for arterial thrombotic disease in young Brazilian patients. 1665 69

Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations were examined. Compared with controls, patients with migraine had higher levels of post-methionine load homocysteine values (19.5 +/- 4.9 vs. 16.9 +/- 1.9; P = 0.025) and significantly lower folate levels (5.8 +/- 2.6 vs. 7.5 +/- 2.1; P = 0.002). We found a trend toward an increased risk of migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be related to migraine in the young, whereas the biochemical differences between migrainous patients and controls are an appealing topic for further investigation.
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PMID:Metabolic and genetic risk factors for migraine in children. 1668 13

Stroke is a very frequent entity. It is the third leading cause of death and the leading cause of adult disability in the developed world. At a population level, the common sporadic form of ischaemic stroke is underpinned by both environmental and genetic risk factors. Typically, in clinical practice, environmental risk factors such as hypertension, diabetes mellitus, smoking, alcohol consumption, and other factors, are usually considered to be more important than genetic factors. However, it is the interplay of both environmental and common genetic factors [such as the Leiden V, methylenetetrahydrofolate reductase C677T, apolipopotein E 4, endothelial nitric oxide synthase G894T, angiotensin-converting enzyme I/D and angiotensin II type 1 receptor A1166C mutations and polymorphisms] that leads to the development of ischaemic stroke. Indeed, a complex network of interactions between genetic factors and clinical risk factors can be supposed. This review evaluates the possible roles of gene-gene and gene-environment interactions concerning the above genetic factors in the evolution of ischaemic stroke and leukoaraiosis. A knowledge of the specific genetic patterns which are associated with a significant risk of ischaemic stroke or leukoaraiosis may also draw attention to a large population at an increased risk of circulatory disorders. This may facilitate the choice of more effective and specific prevention on the basis of the genotype.
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PMID:Gene-gene and gene-environment interplay represent specific susceptibility for different types of ischaemic stroke and leukoaraiosis. 1678 9

The role of homozygosity for the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene as an independent risk factor for primary and recurrent stroke has been questioned, although recent data appear to be supportive. However, the association of homozygous C677T MTHFR mutation with silent brain infarctions in infancy has not been reported. The authors describe an 11-month-old male who had suffered a silent brain infarction followed by a symptomatic arterial stroke. The evaluation revealed mildly elevated homocysteine levels secondary to homozygous C677T alleles for MTHFR and iron deficiency anemia. An extensive evaluation for other causes of infarction was negative. We suggest that the mother's homozygous MTHFR status played a role in the early onset of stroke and that iron deficiency anemia may have contributed to the recurrence. The patient was treated with anticoagulation therapy, folic acid, and iron supplementation and has not had a recurrent event during 3 years of follow-up. This case provides further evidence that homozygous MTHFR mutation is a predisposing factor for early and recurrent pediatric stroke, including silent infarcts, especially in the presence of other risk factors.
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PMID:Homozygous MTHFR C677T gene mutation and recurrent stroke in an infant. 1681 86

Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, beta-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.
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PMID:The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease. 1690 20

Growing evidence indicates that elevated total homocysteine (tHcy) levels can elicit autoimmune response in vivo. Antibodies against Nepsilon-Hcy-proteins have been shown to be associated with stroke and premature myocardial infarction. The aim of the current study was to investigate the effect of treatment with folic acid on anti-Nepsilon-Hcy-albumin and -hemoglobin antibodies. We recruited 20 apparently healthy men and 12 male patients with documented coronary artery disease (CAD). All participants had plasma fasting tHcy levels >15 microM. At baseline, and after three and six months of treatment with folic acid 1 mg daily, we determined tHcy, serum folate and vitamin B12 levels, along with serum anti-Nepsilon-Hcy-albumin and -hemoglobin IgG antibodies using the home-made immunoenzymatic assays. Both groups did not differ with regard to age, tHcy, folate, lipid profile, and CRP. The only significant difference between healthy subjects and CAD patients was levels of antibodies against Nepsilon-Hcy-albumin. As expected, folic acid administration led to significant decreases in tHcy and increases in folate levels in both groups. Levels of both anti-Nepsilon-Hcy-albumin and -hemoglobin antibodies fell markedly following a three-month folic acid administration in healthy subjects, but not in CAD patients, without any changes at six months in either group. Folic acid administration resulted in a loss of significant correlations between tHcy and antibodies both following three and six months of the therapy in healthy subjects, in contrast to CAD patients. Carriers of the methylenetetrahydrofolate reductase (MTHFR) 677T allele with CAD had significantly higher levels of anti-Nepsilon-Hcy-albumin before and during folic acid administration as compared to healthy subjects. In conclusion, our findings suggest that Hcy-related autoimmune response is resistant to folic acid administration in CAD patients, while in healthy subjects reduced tHcy levels are associated with suppressed production of antibodies against Nepsilon-Hcyproteins. These observations might explain at least in part the failure of vitamin therapy to reduce the risk of cardiovascular events as recently reported.
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PMID:Folic acid administration and antibodies against homocysteinylated proteins in subjects with hyperhomocysteinemia. 1695 77

We describe the anesthetic management of a patient with placenta previa presenting for a cesarean section, who had methylenetetrahydrofolate reductase (MTHFR) deficiency. Methylenetetrahydrofolate reductase deficiency increases homocysteine levels in the body and, therefore, predisposes to thrombosis. After a cerebrovascular accident at 8 weeks of gestational age, the patient received anticoagulants throughout the course of her pregnancy. Bleeding from the placenta previa occurred at 30 weeks of gestational age. Although general anesthesia was indicated for this patient because of her hemodynamic instability and an anticoagulated state, nitrous oxide is contraindicated in such patients. Thus, we chose a subarachnoid block because the patient remained hemodynamically stable, and anticoagulation had been stopped 8 hours before surgery. To our knowledge, there is no reported case of a parturient with MTHFR deficiency complicated with a cerebrovascular accident and associated with placenta previa presenting for a cesarean section. Anesthetic considerations are discussed in patients presenting with placenta previa associated with MTHFR deficiency.
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PMID:Anesthesia for cesarean section in a patient with placenta previa and methylenetetrahydrofolate reductase deficiency. 1698 Jan 65

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.
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PMID:Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C. 1711 27


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