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

---

Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.
...
PMID:Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam study. 1139 38

Elevated plasma homocysteine is a new risk factor for atherosclerotic vascular disease resulting in progressive atherogenesis in the arteries of the limbs, the coronary arteries and the cerebrovascular system. Hyperhomocysteinemia may be induced by failure or decreased enzyme activity of the cystathionine-beta-synthase and methylenetetrahydrofolate reductase due to genetic mutation or deficiency of folic acid, vitamin B12 and vitamin B6. Oxidation of homocysteine to homocystine is accompanied with production of hydrogen peroxide inducing damage of endothelium through oxidative stress. The injury of the endothelium by homocysteine can be shown by measuring flow-induced vasodilation in men. The abnormalities of coagulation found in hyperhomocysteinemia is related to the impairment of the function of endothelial cells and inhibition of the thrombomodulin-protein C and glycosaminoglycan-antithrombin-III anticoagulant system. Homocysteine decreases the level of glutathione peroxidase in the endothelial cells, and inhibits its activation leading to the impairment of oxidative defensive mechanism, and to the free radical-induced NO-inactivation. In decreasing of plasma homocysteine level and preventing its influence on endothelium, moreover in improving of endothelial function the folic acid has cardinal importance, however the vitamin B12 and vitamin B6 also play role in the maintenance of normal homocysteine level of blood.
...
PMID:[Homocysteine--a risk factor for atherosclerosis]. 1148 6

The relationship between hyperhomocysteinemia and coronary artery disease (CAD) was investigated and the influence of environmental factors (Folate, VitB12) and genetic factors [N5, N10-methylenetetrahydrofolate reductase gene (MTHFR) or MTHFR gene mutation] on plasma homocysteine (Hcy) levels and the risk of CAD observed. Fifty-one CAD patients and 30 CAD-free subjects were recruited in the study. The polymorphisms of MTHFR gene were analyzed by PCR-RFLP and plasma total Hcy levels were measured by high performance liquid chromatography with fluorescence detection. Plasma folate and vitamin B12 concentrations were measured by an automated chemiluminescence method. It was found that mean total plasma Hcy concentrations were significantly higher in CAD patients than in CAD-free subjects (P < 0.01). The differences were also apparent among the three genotypes of MTHFR gene in CAD group (P < 0.05). There was no significant difference in the genotype distributions and allele frequencies between the two groups. A strong inverse correlation was found between folate or vitamin B12 and plasma Hcy levels according to MTHFR genotype (P < 0.01). It was concluded that hyperhomocysteinemia is a new independent risk factor for CAD. However, MTHFR gene mutation alone does not relate significantly to the morbidity of CAD since hyperhomocysteinemia and its influence on the risk of CAD are decided by both environmental and genetic factors. Supplementary treatment with vitamins B can effectively lower the plasma levels of Hcy, thus maybe reducing the risk of CAD.
...
PMID:The effect of polymorphisms of MTHER gene and vitamin B on hyperhomocysteinemia. 1152 37

Glomerular filtration is one of the major determinants of plasma total homocysteine (tHcy). To evaluate the respective roles of residual glomerular filtration (by measuring a specific protein marker, cystatin C), genetic polymorphisms and nutritional status in tHcy blood levels in end-stage renal disease patients (ESRD) under hemodialysis and supplemented with folate, we measured tHcy, folate, vitamin B12 (B12), creatinine, cystatin C, albumin and C-reactive protein and determined the polymorphism of methylenetetrahydrofolate reductase (MTHFR) (C677T and A1289C) and of methionine synthase (MS) (A2756G) in 114 ESRD patients before hemodialysis and 76 control subjects. All patients received a folate supplementation of 700 microg/day. Hyperhomocysteinemia was observed in all patients and exceeded the upper normal limit by 2-fold in 52.4% of the patients. Serum folate was significantly increased and the B12 level was not different from controls. Folate, Cystatin C and creatinine were significantly correlated to tHcy, while no correlation was found between tHcy, albumin and C-reactive protein. No difference in genotype frequency between ESRD patients and controls was found for MTHFR A1289C and MS A2756G. The MTHFR 677TT genotype was less frequent and was associated with a significantly higher tHcy level in patients. Folate and residual glomerular filtration estimated by cystatin C and creatinine levels were two independent determinants of tHcy in ESRD patients. These data suggest that hyperhomocysteinemia is a consequence as well as a complicating factor of renal failure.
...
PMID:Hyperhomocysteinemia is related to residual glomerular filtration and folate, but not to methylenetetrahydrofolate-reductase and methionine synthase polymorphisms, in supplemented end-stage renal disease patients undergoing hemodialysis. 1159 45

Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 micromol/l vs 6.8 micromol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 micromol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 micromol/l) than nondialyzed patients with the mutation (10.7 micromol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l. Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients.
...
PMID:Plasma homocysteine concentration in children with chronic renal failure. 1160 87

Cardiovascular disease (CVD) is the principle cause of death in patients with end-stage renal disease. Some gene polymorphisms and hyperhomocysteinemia have been implicated in the pathogenesis of CVD. The aim of this study was to assess the relationships between angiotensin-converting enzyme genotype, endothelial nitric oxide synthase genotype, and methylenetetrahydrofolate reductase (MTHFR) genotype and CVD in patients on hemodialysis and to clarify the determinants of plasma homocysteine level. One hundred and sixty-eight patients on hemodialysis (87 males and 81 females, mean age 60.7 +/- 13.1 years) were included. A history of CVD was present in 25% of the patients. There was a significant difference in the distributions of MTHFR non-VV genotype and MTHFR VV genotype between patients with a CVD history and patients without a CVD history, but no difference in the distributions of angiotensin-converting enzyme genotypes and endothelial nitric oxide synthase genotypes. The plasma homocysteine concentration was significantly higher in patients with MTHFR VV genotype than in patients with MTHFR non-VV genotype. The plasma homocysteine concentration was negatively correlated with plasma vitamin B12 concentration and plasma folate concentration. On stepwise multiple-regression analysis for the predictors of plasma homocysteine concentration, MTHFR VV genotype and gender were significant. In conclusion, MTHFR polymorphism may be a risk factor for CVD in patients on hemodialysis, and MTHFR VV genotype and gender may be strong determinants of the plasma homocysteine level.
...
PMID:Methylenetetrahydrofolate reductase gene polymorphism, hyperhomocysteinemia, and cardiovascular diseases in chronic hemodialysis patients. 1174 4

Elevated total plasma homocysteine has been established as an independent risk factor for thrombosis and cardiovascular disease. A strong relationship between plasma homocysteine levels and mortality has been reported in patients with angiographically confirmed coronary artery disease. Homocysteine is a thiol containing amino acid. It can be metabolised by different pathways, requiring various enzymes such as cystathionine beta-synthase and methylenetetrahydrofolate reductase. These reactions also require several co-factors such as vitamin B6 and folate. Medications may interfere with these pathways leading to an alteration of plasma homocysteine levels. Several drugs have been shown to effect homocysteine levels. Some drugs frequently used in patients at risk of cardiovascular disease, such as the fibric acid derivatives used in certain dyslipidaemias and metformin in type 2 (non-insulin-dependent) diabetes mellitus, also raise plasma homocysteine levels. This elevation poses a theoretical risk of negating some of the benefits of these drugs. The mechanisms by which drugs alter plasma homocysteine levels vary. Drugs such as cholestyramine and metformin interfere with vitamin absorption from the gut. Interference with folate and homocysteine metabolism by methotrexate, nicotinic acid (niacin) and fibric acid derivatives, may lead to increased plasma homocysteine levels. Treatment with folate or vitamins B6 and B12 lowers plasma homocysteine levels effectively and is relatively inexpensive. Although it still remains to be demonstrated that lowering plasma homocysteine levels reduces cardiovascular morbidity, surrogate markers for cardiovascular disease have been shown to improve with treatment of hyperhomocystenaemia. Would drugs like metformin, fibric acid derivatives and nicotinic acid be more effective in lowering cardiovascular morbidity and mortality, if the accompanying hyperhomocysteinaemia is treated? The purpose of this review is to highlight the importance of homocysteine as a risk factor, and examine the role and implications of drug induced modulation of homocysteine metabolism.
...
PMID:Drugs affecting homocysteine metabolism: impact on cardiovascular risk. 1189 29

Hyperhomocysteinemia is an independent risk factor for vascular disease, frequently observed in patients with severe renal impairment. Hyperhomocysteinemia has never been considered as a possible risk factor in renal artery stenosis. We investigated plasma folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine beta-synthase (CBS) 844ins68 polymorphisms, and homocysteine levels before and after methionine (100 mg/kg) loading in 58 patients with angiographically documented renal artery stenosis and mildly impaired renal function. One hundred and two normotensive subjects with angiographically normal coronary arteries and no history or clinical or angiographic evidence of atherosclerosis in other vascular districts, were considered as a control group. Mean total homocysteine levels were significantly higher in patients than in controls (P<0.01), as was the prevalence of hyperhomocysteinemia (51.7% vs. 32.3%, P<0.05). However, MTHFR alleles and genotypes as well as CBS 844ins68 mutation frequencies were similar in the two groups, whereas a lower folate level was observed in the patients. Moreover, patients with MTHFR A/A genotype showed a poorer folate status than control subjects, suggesting that a subclinical folate deficiency may be very frequent in renal artery stenosis, regardless of C677T mutation. In conclusions, hyperhomocysteinemia is common in patients with atheromatous renal artery stenosis; a subclinical folate deficiency seems to be involved, regardless of MTHFR thermolabile or CBS insertion genotypes. Folate supplementation might be useful in the management of overall vascular risk of these patients.
...
PMID:Homocysteine and atheromatous renal artery stenosis. 1191 80

Hyperhomocysteinemia is a defined risk factor for venous thromboembolism (VTE). Several polymorphisms of genes encoding for enzymes acting in the remethylation pathway of homocysteine metabolism, ie, methionine synthase (MS) A2756G, methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C, can cause increased homocysteine levels particularly in patients with deficiencies of folic acid, vitamin B6, or B12 and hence be potential risk factors for VTE. Indeed, homozygous MTHFR C677T was shown to be a mild risk factor for VTE by some, but not by all, investigators. In this study, we assessed the risk exerted by MS A2756G and MTHFR A1298C in a cohort of patients with idiopathic venous thromboembolism. Homozygosities for MS A2756G and MTHFR A1298C were not found to be statistically significant risk factors for VTE. In addition, no interactions were observed among MS A2756G, MTHFR A1298C and MTHFR C677T in conferring a risk of VTE.
...
PMID:Methionine synthase A2756G and methylenetetrahydrofolate reductase A1298C polymorphisms are not risk factors for idiopathic venous thromboembolism. 1192 Feb 32

Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.
...
PMID:Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients. 1197 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---