L-methylfolate, a new option in psychiatric treatment, would it be linked to psoriasis relapse? / L-metilfolato, uma nova opção no tratamento psiquiátrico, estaria ligado à recaída de psoríase?

ABSTRACT We report a case of a 61-years-old woman in remission of psoriasis for 20 years. She presented recurrence of psoriasis in the form of plaques few days after taking L-methylfolate 15mg/day. The L-methylfolate was prescribed as an adjuvant for the treatment of depression in a patient with the methylenetetrahydrofolate reductase gene polymorphism (MTHFR).

RESUMO Paciente do sexo feminino, 61 anos, em remissão da psoríase por 20 anos. Apresentou recidiva de psoríase em forma de placas poucos dias após início de tratamento L-metilfolato na dose diária de 15mg. O L-metilfolato foi prescrito como terapêutica coadjuvante para tratamento de depressão em paciente portadora do polimorfismo do gene metilenotetrahidrofolato redutase.

Folates retention in brassica vegetables consumed in Brazil after different cooking methods / Retención de folatos en hortalizas consumidas en Brasil después de diferentes métodos de cocción

The present study aimed to determine the effects of different traditional cooking methods on folate (tetrahydrofolate - THF, 5-methyltetrahydrofolate - 5- MTHF and 5-formyltetrahydrofolate - 5-FTHF) retention in leafy vegetables. The analysis of folates was carried out by high performance liquid chromatography (HPLC), with detection by fluorescence, using gradient elution, mobile phase of acetonitrile and phosphate buffer solution. The retention of isomers in vegetables after cooking ranged from 17.0 % to 87.2 % for THF, 53.4 - 94.1% for 5-MTHF and 39.0 - 107.9% for 5-FTHF. The retention of folates depended on the food matrix, the kind of isomer, and the cooking methods used. It is recommended that one should have more control over the choices for methods and time of cooking and the amount of water used at home and at foodservice as well.

El presente estudio tuvo como objetivo determinar los efectos de los diferentes métodos de cocción tradicionales sobre la retención de folatos (tetrahidrofolato - THF, 5-metiltetrahidrofolato - 5- MTHF y 5-formiltetrahidrofolato - 5 FTHF) en hortalizas. El análisis de folatos se llevó a cabo por cromatografía líquida de alta resolución (CLAR), con detección por fluorescencia, usando elución en gradiente, fase móvil de acetonitrilo y solución tampón de fosfato. La retención de los isómeros en las hortalizas después de la cocción varió de 17,0% a 87,2% para THF, 53,4 a 94,1% para 5-MTHF y de 39,0 a 107,9% para 5- FTHF. La retención de folatos dependió de la matriz del alimento, el tipo de isómero, y los métodos de cocción utilizados. Se recomienda que uno debe tener más control sobre las opciones de métodos y tiempo de cocción y la cantidad de agua utilizada en el hogar y también en los servicio de alimentación.

Methylenetetrahydrofolate reductase gene polymorphism in coronary artery disease patients

Coronary artery disease occurs with the interact ion between environmental influences and genetic factors. Genetic susceptibility may be caused by mutations and polymorphisms in a variety of genes mainly involved in blood coagulation, metabolism of lipids, homocysteine and or iron. The most common form of genetic hyperhomocysteinemia results from the production of a thermolabile variant of methylene tetrahydrofolate reductase [MTHFR] with reduced enzymatic activity. This study was performed on ninety individuals selected with normal serum glucose, kidney, liver, and thyroid function test and lipid profile. They classified into: Group I: 27 apparently healthy persons as control group. Group II: 3 apparently healthy persons with elevated homocysteine level. Group III: 27 CAD patients with normal coronary angiography. Group IV: 33 CAD patients with abnormal coronary angiography. The following specific investigations were done for all the studied persons:- Serum homocysteine [Hcy], serum folic acid [FA] and MTHFR genotyping by PCR-RFLP

Results: In group III three patients had elevated Hey [11.1%]. There was significant elevation of Hey level in group IV compared to group I [P<0. 05].however there were insignificance differences in mean value of folic acid of the studied groups compared to each other. As regard the relation between the MTHFR polymorphisam and hey and FA levels, in group I there was significant elevation of serum Hey level in carriers of CT genotype compared to carriers of CC genotype [P<0.05]. Homocysteine level was highly elevated in patients had TT genotype in group III and group IV when compared to CC and CT genotypes and this was statistically highly significant [<0.000] in group IV, but insignificant elevation in group III Folic acid level was not differing between patients had TT genotype when compared to CC and CT genotype in all studied groups and that was statistically insignificant. When we study the severity of CAD in group IV there was insignificant elevation of serum Hey level in group of one vessel affection compared to group of two vessel and multi vessel affection, there was Significant elevation of serum Hey level in group of >/= 90% stenosis compared to group of >50-75% stenosis and 75-90% stenosis. However there was insignificant difference in serum FA between the groups compared to each other. Homozygous TT was detected in group of one vessel affection and with >90% stenosis. Carriers of TT genotypes in group of one vessel affection and in>/= 90% stenosis had highly significant elevation [P<0.000] of serum homocysteine compared to CC and CT genotypes in the same group

Conclusion: Our findings support that homozygous MTHFR TT genotype is a genetic risk factor for CAD

Livedoid Vasculopathy with Hyperhomocysteinemia due to MTHFR Mutation / 대한피부과학회지

Livedoid vasculopathy is a hyalinizing vascular disease characterized by thrombosis and ulceration of the lower extremities. It can be caused by an alteration in control of coagulation with the formation of thrombi within dermal blood vessels. We report a case of livedoid vasculopathy with hyperhomocysteinemia due to MTHFR mutation, which is treated by folic acid and which also showed very unusual clinical manifestations. A 38-year-old male visited the department of dermatology with a 1 year history of purplish-brown purpura with punched-out ulcers on both lower legs. He had a history of homocysteinemia due to methylene tetrahydrofolate reductase (MTHFR) mutation. The histopathologic findings of the lesional skin revealed dense superficial and deep perivascular and perifollicular infiltrates of lymphocytes and fibrin deposition within the vessels in the dermis. On the basis of clinical and pathological findings, livedoid vasculopathy with hyperhomocysteinemia due to MTHFR mutation was diagnosed and improved by the treatment of 1 mg of folic acid daily.

Purification and activity evaluation of methionine synthase / 药学学报

Methionine synthase (MS, EC2.1.1.13), a key enzyme in the folate metabolism area catalyzing methyl transfer from N5-methyltetrahydrofolate to homocysteine to give tetrahydrofolate and methionine, takes a core position in folate cycle, one-carbon-unit transfer and sculpture amino acid pathways. Cobalamin-dependent methionine synthase was purified from rat liver. The enzyme was purified 609-fold to near homogeneity by batch chromatography on DE-52, anion-exchange chromatography on Q Sepharose Fast Flow and CHT-I hydroxyapatite column and was identified by SDS-PAGE and Western blotting. The enzyme activity was determined by spectrophotometric assay. In addition, the influencing factor and optimal reaction condition were performed. The steady state kinetic of rat liver methionine synthase was similar to that of other mammalian cobalamin-dependent methionine synthase which employed a Ping-Pong mechanism. The result indicated that cobalamin-dependent methionine synthase purified from rat liver is suitable for screening and studying methionine synthase specific inhibitors.

Polymorphisms of methylenetetrahydrofolate reductase are not a risk factor for Kawasaki disease in the Korean population / 소아과

PURPOSE: Hyperhomocysteinemia is known as a risk factor for atherosclerosis. Preclinical arteriosclerosis is noted and premature atherosclerosis is known to be accelerated in Kawasaki disease (KD) patients. Genetic polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene result in elevated plasma homocysteine concentrations and are known to be associated with the development of coronary artery disease. Our hypothesis is that single nucleotide polymorphisms (SNPs) of the MTHFR gene are related to the development of KD and coronary artery lesions (CALs). METHODS: For this study, we selected 3 candidate single nucleotide polymorphisms (SNPs) (rs2274976, rs1801131, and rs1801133) of MTHFR. These SNPs are located on chromosome 1p36.3. We included 101 KD patients and 306 healthy adults as controls in this study. CALs were seen in 38 patients. Genotypes of the selected SNPs were determined by direct sequencing and analyzed with SNPAlyze. RESULTS: The genetic distribution and allelic frequency of the 3 MTHFR SNPs (rs2274976, rs1801131, and rs1801133) were not significantly different in patients with KD compared to the control group (P=0.71, 0.17, and 0.96, respectively). There was no difference in the genetic distribution of the MTHFR SNPs between the normal control group and the CAL group (P=0.43, 0.39, 0.52 respectively). CONCLUSION: The genetic distribution of the MTHFR SNPs (rs2274976, rs1801131, and rs1801133) was not different in the KD group compared to the control group. In addition, the genetic distribution of these SNPs was not different in the CAL group compared to the control group in the Korean population.

Association between polymorphism of MTHFR gene and non-familial colorectal cancer

Colorectal cancer is one of the most common malignancies in worldwide. Because the gene 5, 10-methylene-tetrahydrofolate reductase [MTHFR] plays a key role in methylation, synthesis and repair of DNA, numerous studies have focused on evaluating the correlation between polymorphisms of this gene and sporadic colorectal cancer. This study was carried out to examine the association of MTHFR gene polymorphism, C677T, with non-familial colorectal cancer in an Iranian population. We analyzed peripheral blood samples of 118 cases of colorectal cancer and 189 controls by pyrosequencing method. Controls were subjects who had been referred to our center during the study period and had revealed normal findings on colonoscopy. We found that frequency of CC, CT and TT genotypes among the colorectal cancer patients were 51.7%, 28% and 20.3% respectively. The figures for controls were 47.1%, 27% and 25.9% respectively. Furthermore, allele frequency T in the cases was 34% and allele frequency C was 66% while allele frequency T in controls was 39% and allele frequency C was 61%. Interestingly we observed a reverse association between risk of colon cancer with 677TT genotype

Polymorphism of the 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Gene and Microsatellite Instability (MSI) in Mucinous Colorectal Cancer

PURPOSE: Generally, a mucinous carcinoma (Muc) of the colon show higher rates of microsatellite instability (MSI) than a non-mucinous carcinoma (non-Muc). Mutated methylenetetrahydrofolate reductase (MTHFR) brings about low enzyme activity, which may reduce genomic DNA methylation. These processes may be critical for the oncogenic transformation of human cells. We compared the relationship of MSI and MTHFR polymorphism in Muc to that in non-Muc. METHODS: From March 2003 to August 2007, genomic DNA was isolated from whole blood and tissue specimens of 285 colorectal cancer patients (Muc: 31 cases, non-Muc: 254 cases) and 448 normal control patients. These were subjected to MSI analysis and MTHFR genotyping by using PCR-based restriction fragment length polymorphism analyses. RESULTS: MSI was significantly more frequent in the Muc group (40.7%) than in the non- Muc group (14.8%). The frequencies of polymorphism of MTHFR 677C>T were CC (31.5%), CT (57%), and TT (11.5%) in the patient group and 32.4%, 53.1%, and 14.5% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 677C>T were CC (36%), CT (56%), TT (8%), and in the non-Muc group, they were 31.1%, 57%, and 11.9%. The frequencies of polymorphism of MTHFR 1298A>C were AA (73%), AC (21.3%), and CC (5.7%) in the patient group and 69.6%, 28.6%, and 1.8% in the control group. In the Muc group, the frequencies of polymorphism of MTHFR 1298A>C were AA (50%), AC (30%), and CC (20%), and in the non-Muc group, they were 76%, 20.3%, and 3.7%. The Muc group showed higher frequencies of the CC variant than the non-Muc group (P-value=0.018). No relation between MSI and MTHFR polymorphisms were seen in any comparison of the Muc and the non-Muc groups. CONCLUSIONS: The Muc group showed higher rates of MSI than the non-Muc group, but no definite difference between the Muc and the non-Muc groups was noted in the case of polymorphism of MTHFR 677C>T. However, the TT-type variant showed slightly lower frequencies in the Muc group than in the non-Muc group. On the contrary, the Muc group showed a higher rate of the CC variant in polymorphism of MTHFR 1298A>C. These inconsistent results seem to be due to the small size of the Muc group, so further study is needed.

Methylenetetrahydrofolate Reductase Gene C677T Mutation and Apolipoprotein E Gene Mutation in Recurrent Aphthous Stomatitis / 대한피부과학회지

BACKGROUND: Recurrent aphthous stomatitis (RAS) is usually the earliest sign of Behcet's disease. Hyperhomocysteinemia can damage endothelial cells and progress to obstructive vascular disease. It has been reported that hyperhomocysteinemia is a marker of activation in Behcet's disease. Enzyme 5,10-methylenetetrahydrofolate reductase may be one of the main factors that regulates plasma homocysteine levels. Homozygosity for the C677T (MTHFR C677T) mutation is associated with reduced activity of this enzyme and considered the most common genetic cause of elevated serum homocyteine levels. However its relationship to vascular injury in Behcet's disease remains controversial, and its relationship to RAS is unknown. Apolipoprotein E (Apo E) has both immunoregulatory and anti-infective features. Search for Apo E polymorphism and lipid composition in RAS patients might be a clue to pathogenesis of RAS. OBJECTIVE: To analyze the relationship of MTHFR gene C677T polymorphism, several epidemiologic factors such as age and sex, smoking, lipid composition and Apo E polymorphism to vasculitis in RAS, we assessed the MTHFR gene C677T polymorphism, Apo E polymorphism and lipid composition in RAS and normal population. METHODS: We analyzed data from the General Health survey conducted on 1,243 participants (M:F=281:962) over a 20 year-old in Incheon city. Medical interview and laboratory test for methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, apolipoprotein E polymorphism were completed. Statistical significance was analyzed by chi-square test and multistep logistic regression analysis. RESULTS: Among normal population over the age of twenty, a total of 34.2% (426/1,243) had RAS. Female predominance (4.5:1, p=0.003) was noted. The incidence of RAS in age group 20 to 39 year old is higher than the over 40 age group. The incidence is higher in smoking group compared to the nonsmoking group in multistepwise logistic regression analysis. Frequency of the MTHFR C677T genotypes was highest at CT compared to CC and TT homozygous genotype in normal and RAS patients group. There was no significant statistical differences in MTHFR genotypes in RAS patients compared to the control group. Similarly, Apo E genotype analysis revealed no significant statistical differences either. Apo E genotype and total cholesterol, HDL-cholesterol, triglyceride level didn't show any associations. CONCLUSION: This study revealed insignificant association between the MTHFR C677T mutation and RAS. Apo E genotype didn't show a significant statistical difference in RAS patients compared to normal controls.

Neural tube defects: pathogenesis and folate metabolism.

Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex aetio-pathogenesis. Animal studies indicate that there may be four sites of initiation of neural tube closure (NTC). Selective involvement of these sites may lead to defects varying from anencephaly to spina bifida. The NTC involves formation of medial and dorsolateral hinge points, convergent extension and a zipper release process. Proliferation and migration of neuroectodermal cells and its morphological changes brought about by microfilaments and other cytoskeletal proteins mediate NTC. Genetic, nutritional and teratogenic mechanisms have been implicated in the pathogenesis of NTDs. Folate is an important component in one carbon metabolism that provides active moieties for synthesis of nucleic acids and proteins. Several gene defects affecting enzymes and proteins involved in transport and metabolism of folate have been associated with NTDs. It may be possible in future, to identify individuals at higher risk of NTDs by genetic studies. Epidemiological and clinical studies have shown that dietary supplementation or food fortification with folic acid would reduce the incidence of NTDs. The protective effect of folic acid may be by overcoming these metabolic blocks through unidentified mechanisms. Genetic and biochemical studies on foetal cells may supplement currently available prenatal tests to diagnose NTDs. Antiepileptic drugs (AEDs), particularly valproate and carbamazepine have been shown to increase the risk of NTDs by possibly increasing the oxidative stress and deranging the folate metabolism. Accordingly, it is recommended that all women taking AEDs may use 1-5 mg folic acid daily in the pre conception period and through pregnancy.

Homozygous VN (677C to T) and d/D (2756G to A) variants in the methylenetetrahydrofolate and methionine synthase genes in a case of hyperhomocysteinemia with stroke at young age

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.