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)

Migraine is a common form of the chronic headache syndromes. Although the pathogenesis of migraine still remains enigmatic, there have been remarkable progress in headache research. Point mutations of P/Q-type Ca2+ channel alpha 1 subunit (CACNA1A) gene have been identified in familial hemiplegic migraine (FHM), which linked to chromosome 19 (FHM-1, OMIM 141500). Na-K ATPase alpha2 gene has been identified as the causative gene for FHM linked to 1q21-23 (FHM-2, OMIM 602481). Common forms of migraine (i.e. migraine with and without aura) seems to be caused from multifactorial genetic factors and environmental factors. An association study of allelic variation at Codon 23 (Cys or Ser) of 5HT2C-R gene in Japanese samples revealed that the Ser allele frequency in migraine with aura was significantly higher than that in the non-headache controls. However, negative association of this polymorphism have been reported in Caucasian migrainures. The C677T allelic variation of 5,10-methylenetetrahydrofolate reductase (MTHFR) are focused on in association with the coronary heart diseases and the cerebrovascular diseases. The T allelic frequency in migraine sufferers was significantly higher than that in controls. The C677T mutation of MTHFR is one of the genetic risk factors for migraine. These observations are confirmed in Turkish, Australian and Spanish samples. Positive associations of angiotensin converting enzyme (ACE) gene, endotheline receptor-A (ET-A) gene, and insulin receptor gene have been reported. Using the genomewide screen technology, significant linkage between the migraine with aura and a marker on 4q24 has been reported in Finnish families. The genome wide screen analysis will be one of the powerful strategies on exploring migraine gene. Genetic study of migraine headache is a promised and fruitful field and will provide deep understanding to migraine headache. Discovery of new responsible or susceptible genes to migraine will also open an avenue to develop new therapeutic strategy of migraine.
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PMID:[An update on the familial headache syndromes]. 1565 39

Recent advances in genetic analysis of migraine headache are reviewed. Point mutations of P/Q -type Ca2+ channel alpha1 subunit(CACNA1A) gene and Na-K ATPase, alpha2 (ATP1A2) gene have been identified in the familial hemiplegic migraine (FHM-1 and FHM-2, respectively). Mutations in notch-3 gene cause the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an autosomal dominant inherited disorder often accompanying with migraine like headache. Serotonin (5-HT) related genes, dopamine D2 receptors (DRD2) gene, methylenetetrahydrofolate reductase (MTHFR) gene, and angiotensin converting enzyme (ACE) gene have been noticed as the susceptible genes for migraine pathogenesis. Genetic study of migraine is promising and will provide further understanding of the migraine pathophysiology. Discovery of the responsible or susceptible genes will open an avenue to develop new therapeutic strategy.
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PMID:[Genetic analysis of migraine headache: a review]. 1621 82

The active site of oxidative phosphorylation and adenosine triphosphate (ATP) synthesis in mitochondria is proposed to consist of two molecules of thioretinamide bound to cobalamin, forming thioretinaco, complexed with ozone, oxygen, nicotinamide adenine dinucleotide. and inorganic phosphate, TR2CoO3O2NAD(+)H2PO4(-). Reduction of the pyridinium nitrogen of the nicotinamide group by an electron from electron transport complexes initiates polymerization of phosphate with adenosine diphosphate, yielding nicotinamide riboside and ATP bound to thioretinaco ozonide oxygen. A second electron reduces oxygen to hydroperoxyl radical, releasing ATP from the active site. A proton gradient is created within F1F0 ATPase complexes of mitochondria by reaction of protons with reduced nicotinamide riboside and with hydroperoxyl radical, yielding reduced nicotinamide riboside and hydroperoxide. The hyperhomocysteinemia of aging and dementia is attributed to decreased synthesis of adenosyl methionine by thioretinaco ozonide and ATP, causing decreased allosteric activation of cystathionine synthase and decreased allosteric inhibition of methylenetetrahydrofolate reductase and resulting in dysregulation of methionine metabolism.
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PMID:The active site of oxidative phosphorylation and the origin of hyperhomocysteinemia in aging and dementia. 2588 81

Wilson disease (WD) is characterized by remarkable variety in its phenotypic presentation. Patients with WD can present with hepatic, neurologic, and psychiatric symptoms combined in different and unpredictable ways. Importantly, no convincing phenotype-genotype correlation has ever been identified, opening the possibility that other genes, aside from ATPase copper-transporting beta (ATP7B), are involved in the pathogenesis of this condition. In addition, modifier genes, or genes that can affect the expression of other genes, may be involved. Clinical and basic science data indicate that environmental and dietary factors can potentially modify gene expression in WD and, consequently, its clinical presentation and course. In particular, previously studied genes include copper metabolism domain-containing 1 (COMMD1), antioxidant 1 copper chaperone (ATOX1), X-linked inhibitor of apoptosis (XIAP), apolipoprotein E (APOE), hemochromatosis (HFE), and 5,10-methylenetetrahydrofolate reductase (MTHFR). Dietary factors include iron and methyl group donors which could affect methionine metabolism and epigenetic mechanisms of gene expression regulation. Most of the work conducted in this field is in its initial stages but it has the potential to change the diagnosis and treatment of WD.
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PMID:Genetic and environmental modifiers of Wilson disease. 2843 8