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)

Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). It is recognized that a hypercoagulable state exists in IBD which involves all components of the clotting system. It has been suggested that this hypercoagulable state is closely linked to the disease pathogenesis. Recent studies have shown that genetic defects such as factor V Leiden mutation and C677T methylenetetrahydrofolate reductase polymorphism associated with hyperhomocysteinemia seem to interfere in the thrombotic manifestations of IBD. Acquired factors such as antiphospholipid antibodies could also participate in the development of the thrombotic process. Deficiencies of other anticoagulant factors play a less important role in the thrombosis, and therefore it is not surprising that the results on these factors in IBD are contradictory. In conclusion the resultant gene-gene and gene-environment interactions between risk factors are the key to the understanding of why an IBD patient develops thrombosis at a specific point in time.
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PMID:Role of thrombotic vascular risk factors in inflammatory bowel disease. 1127 34

Individuals with inflammatory bowel disease frequently experience increased systemic thromboembolic complications, which represent an important cause of morbidity and mortality. Risk factors for thrombosis can be inherited or acquired. The most common inherited risk factors for thromboembolism are factor V Leiden mutation, G20210A mutation in the prothrombin gene, and homozygous C677T mutation in the methylenetetrahydrofolate reductase gene. In the last few years, a great amount of literature has focused on the prevalence of such genetic mutations and their role in determining thrombosis in IBD patients. In this review, we summarize the results of these studies.
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PMID:Review article: inherited thrombophilia in inflammatory bowel disease. 1281 64

Azathioprine, mercaptopurine, methotrexate, ciclosporin and tacrolimus all have their respective niches in the treatment of inflammatory bowel disease. These immunomodulators are potent and effective medications; however, they potentially have serious toxicity. To maximize benefit and minimize risk, clinicians must understand the mechanism of action, appropriate indications, range of toxicity and proper dosing of these medications. Furthermore, once initiating therapy, patients need to be monitored appropriately for evidence of efficacy and toxicity. This review includes the rationale behind recommendations for the management and monitoring of patients using immunomodulators. For the purine antagonists--azathioprine and mercaptopurine--the evidence for utility of thiopurine methyltransferase testing and mercaptopurine metabolite monitoring is addressed. The roles of liver biopsy and screening for methylenetetrahydrofolate reductase mutations in patients taking methotrexate are reviewed. With appropriate monitoring, the calcineurin inhibitors--ciclosporin and tacrolimus--can be used safely and effectively. Immunomodulators are important agents for the treatment of Crohn's disease and ulcerative colitis, and prescribing clinicians should be comfortable recognizing both their value and their limitations.
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PMID:Review article: practical management of inflammatory bowel disease patients taking immunomodulators. 1596 74

Inflammatory bowel disease (IBD) has been related to mutations of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in the metabolism of folate and methionine, both of which are important factors in DNA methylation and synthesis. A mutated MTHFR genotype was associated with increased toxicity of methotrexate treatment. The objective of this study was to verify, in a population of young patients with IBD, the presence of an association among mutations in the MTHFR gene, the incidence of IBD, and the risk of adverse events during the treatment with thiopurines azathioprine (AZA) or 6-mercaptopurine (6MP). Ninety-two patients with IBD were enrolled; 63 were treated with thiopurines; patients and 130 controls were genotyped for MTHFR mutations by PCR-based methods. The incidence of mutations in the MTHFR gene was not different between patients with IBD and control subjects; the mutated genotype was not associated with an increased risk of toxicity during thiopurine treatment.
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PMID:Prevalence of methylenetetrahydrofolate reductase polymorphisms in young patients with inflammatory bowel disease. 1661 55

Moderate hyperhomocysteinemia is a complex trait commonly associated with inflammatory bowel disease (IBD). Nutritional deficiencies and genetic determinants have been identified as risk factors for moderate hyperhomocysteinemia, such as folate and vitamin B(12) deprivation and polymorphisms in the 5,10 methylenetetrahydrofolate reductase (MTHFR) encoding gene, respectively. Homocysteine has a crucial role in cellular stress, epigenetic events, inflammatory processes, and host-microbial interactions. Hyperhomocysteinemia might therefore influence the clinical history of IBD, including disease severity, susceptibility to particular enteric infections, and the risk for the development of colorectal cancer. In contrast, homocysteine metabolism does not seem to contribute to the greater risk of thrombosis in IBD subjects. Herein, we review the evidence linking homocysteine metabolism to the pathophysiology of IBD. Furthermore, we discuss the relevance of screening and treating folate and vitamin B(12) deficiencies in IBD subjects. Given the peculiar frequency of such deficiencies in IBD, normalizing vitamin levels should be an integral part of the management of these patients, especially those with active disease, history of intestinal resection, and/or treated with methotrexate.
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PMID:Vascular and cellular stress in inflammatory bowel disease: revisiting the role of homocysteine. 1735 15

Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Recent data suggest thromboembolism as a disease-specific extraintestinal manifestation of IBD, which is developed as the result of multiple interactions between acquired and genetic risk factors. There is evidence indicating an imbalance of procoagulant, anticoagulant and fibrinolitic factors predisposing in thrombosis in patients with IBD. The genetic factors that have been suggested to interfere in the thrombotic manifestations of IBD include factor V Leiden, factor II (prothrombin, G20210A), methylenetetrahydrofolate reductase gene mutation (MTHFR, 6777T), plasminogen activator inhibitor type 1 (PAI-1) gene mutation and factor XIII (val34leu). In this article we review the current data and future prospects on the role of genetic risk factors in the development of thromboembolism in IBD.
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PMID:Thrombosis and inflammatory bowel disease-the role of genetic risk factors. 1868 Feb 21

Thrombophilia is a rare but potentially catastrophic phenomenon occurring in patients having tendency of thrombosis. It may lead to serious complications. The etiology of thrombophilia is thought to be multifactorial and related to both acquired and inherited factors. Inflammatory bowel disease is an acquired cause of thrombophilia. Thromboembolic events are seen during inflammatory bowel disease, especially during the active period of the disease. In inflammatory bowel disease, thrombus formation in portal, splenic and mesenteric veins are not common. Besides, the association of genetic disorders related to metabolism of homocysteine with inflammatory bowel disease has been evidenced, especially in Crohn disease and rarely in ulcerative colitis. We present a rare case of ulcerative colitis in association with combined portal, splenic and mesenteric vein thrombosis. The patient was recently diagnosed with the disease which was in the inactive period. Interestingly, our patient was also heterozygous for the mutation in methylenetetrahydrofolate reductase (MTHFR) gene.
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PMID:Combined portal, splenic and mesenteric venous thrombosis in inactive ulcerative colitis with heterozygous mutation in MTHFR gene: A rare case of thrombophilia. 2297 54