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)

Polymorphisms in genes can lead to differences in the level of susceptibility of individuals to potentially adverse effects of environmental influences, such as chemical exposure, on prenatal development or male or female reproductive function. We have reviewed the literature in this area, with the caveat that papers involving straight gene knock-outs in experimental animals, without a clear human relevance, were largely excluded. This review represents current knowledge in this rapidly moving field, presenting both human epidemiological and animal data, where available. Among the polymorphic genes and environmental interactions discussed with respect to prenatal development are those for P-glycoprotein (multidrug resistance protein) and the avermectins; methylenetetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, and dietary folic acid; transforming growth factor alpha (TGFalpha) and cigarette smoke; and alcohol dehydrogenase (ADH) and cytochrome P-450 (CYP) 2E1 in association with alcohol consumption. Effects on male reproduction attributable to gene-environment interaction involve infertility seen as a result of either organophosphorous (OP) pesticide interaction with the polymorphic paraoxonase (PON1) gene or antiandrogenic agent interaction with the androgen receptor (AR). MTHFR, folate metabolism, and dietary folic acid are also considered in conjunction with preeclampsia and early pregnancy loss, and the effect of the interaction of glutathione S-transferase (GST) with exposure to benzene or cigarette smoke on pregnancy maintenance is explored. As a conclusion, we offer a discussion of lessons learned and suggested research needs.
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PMID:Gene-environment interactions: a review of effects on reproduction and development. 1560 83

In abdominal aortic aneurysm (AAA) both the etiology and the pathogenesis are of the multifactorial character. The genetic component in the determination of this disease is proven by its familial occurrence. Smoking represents the best recognized risk factor of the AAA development. Increased concentrations of homocysteine (Hcy) in plasma are the common finding in these patients. It is assumed that the Hcy thiolactone, the most reactive metabolite of Hcy, may participate in the aortic wall destruction in AAA. The polymorphic variants of the methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) influence tissue concentrations of the Hcy. Paraoxonase (PON1), the enzyme associated in plasma with the HDL fraction, as lactonase detoxicates the Hcy thiolactone. The promotor polymorphism of PON1 - 108C>T gene may determine the lower activity of this enzyme. In the case-control study of 106 patients with AAA and 97 healthy persons, the effects of selected genetic and nongenetic risk factors on development of AAA were assessed, considering the possibilities of interaction between them. It was found, that the arterial hypertension, cigarette smoking and the lower HDL fraction are independent risk factors of AAA. The arterial hypertension was a risk factor both in the smoking and the nonsmoking males, whereas the lower HDL fraction has been the risk factor only for the smoking men. By the multivariate analysis in the nonsmoking males the MTHFR 1298 AC and CC genotypes increased the risk of AAA development 4,8-fold in relation to the MTHFR 1298 AA nonsmoking males. In reference to the genotypes of the expected high impact on the metabolism of Hcy and of Hcy thiolactone, the genotypes of MTHFR 677TT and PON1 -108CT and TT were more frequent in smoking ones, but the difference was not significant. This observation fits with the assumption that the influence of smoking on the occurrence of AAA prevails over that of genetic variability. When the patients age was considered in the analysis, the PON1 -108CT and TT genotypes were identified as the significant risk factors for the development of AAA in the older smokers.
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PMID:[The different genotypes of MTHFR 1298A>C and PON1 -108C>T polymorphisms confer the increased risk of the abdominal aortic aneurysm in the smoking and nonsmoking persons]. 1652 45

The c.677C>T polymorphism in the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been recently associated with susceptibility to sporadic amyotrophic lateral sclerosis (ALS). We have investigated this association in 450 ALS patients and 700 control subjects from Italy. No significant association was observed at the genotype and allelic level, either for the c.677C>T variant alone or in combination with PON1 polymorphisms. Our negative results suggest that the MTHFR c.677C>T polymorphism is not a risk factor for ALS in the Italian population.
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PMID:No association of MTHFR c.677C>T variant with sporadic ALS in an Italian population. 2186 35

Homocysteine and its modulating genes have strongly emerged as novel biomarkers for coronary artery disease (CAD). In the present study, we investigated whether polymorphisms in homocysteine pathway genes and the plasma levels of homocysteine, folate, and vitamin B12, independently or in combination, are associated with CAD risk. A total of 504 participants were recruited (cases, n = 254; controls, n = 250, respectively). Tetra primer allele refractory mutation system polymerase chain reaction (PCR) was used for resolving the genotypes of 5'10' methylenetetrahydrofolate reductase 'MTHFR' polymorphisms (rs1801133, rs1801131), 5' methyl tetrahydrofolate homocysteine methyltransferase 'MTR' polymorphism (rs1805087), paroxanse1 'PON1' polymorphism (rs662), and cystathionine beta synthase 'CBS' polymorphism (rs5742905). Conventional PCR amplification was carried out for resolving angiotensin converting enzyme 'ACE' insertion/deletion (I/D) polymorphism (rs4646994). ANOVA analysis, adjusted for the covariates, revealed that rs1801133, rs1805087 polymorphisms and homocysteine levels were associated with CAD. Logistic regression analysis (adjusted) revealed similar findings. Logistic regression analysis after applying factorial design to the studied single nucleotide polymorphisms (SNPs) revealed that homocysteine levels and heterozygous and mutant alleles at rs1801133, rs1805087, along with mutant alleles at rs1801131, rs4646994, conferred higher risk for CAD. Our results provide insight into the multifactorial nature of coronary artery disease. We highlight that SNPs in folate pathway genes and homocysteine have role in disease causation and can be used in disease prediction strategies.
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PMID:The communal relation of MTHFR, MTR, ACE gene polymorphisms and hyperhomocysteinemia as conceivable risk of coronary artery disease. 2851 98