scholarly journals Epigenetic Factors in Late-Onset Alzheimer’s Disease: MTHFR and CTH Gene Polymorphisms, Metabolic Trans-sulfuration and Methylation Pathways, and B Vitamins

2018 ◽  
Author(s):  
Gustavo C. Román ◽  
Oscar Mancera-Páez ◽  
Camilo Bernal
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Late Onset ◽  
Memory Loss ◽  
Gene Mutations ◽  
Mthfr Gene ◽  
B Vitamins ◽  
Common Mutation ◽  
Epigenetic Factors ◽  
Vitamin B9 ◽  
Total Homocysteine

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD).  Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss.  MTHFR is critical for production of S-adenosyl-L-methionine (SAM), the principal methyl donor.  A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia – a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B12 (methylcobalamin), vitamin B9 (folic acid), vitamin B6 (pyridoxine), and SAM to patients in early stages of LOAD.

scholarly journals Epigenetic Factors in Late-Onset Alzheimer’s Disease: MTHFR and CTH Gene Polymorphisms, Metabolic Transsulfuration and Methylation Pathways, and B Vitamins

2019 ◽  
Vol 20 (2) ◽  
pp. 319 ◽  
Author(s):  
Gustavo Román ◽  
Oscar Mancera-Páez ◽  
Camilo Bernal
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Methylenetetrahydrofolate Reductase ◽  
Late Onset ◽  
Memory Loss ◽  
B Vitamins ◽  
Common Mutation ◽  
Epigenetic Factors ◽  
Vitamin B9 ◽  
Transsulfuration Pathway

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-l-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the transsulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia—a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B12 (methylcobalamin), vitamin B9 (folic acid), vitamin B6 (pyridoxine), and SAM to patients in early stages of LOAD.

scholarly journals Methylenetetrahydrofolate Reductase C677T and A1298C Mutations in Women with Recurrent Spontaneous Abortions in the Northwest of Iran

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmad Poursadegh Zonouzi ◽  
Nader Chaparzadeh ◽  
Mehrdad Asghari Estiar ◽  
Mahzad Mehrzad Sadaghiani ◽  
Laya Farzadi ◽  
...  
Keyword(s):  
Restriction Fragment Length Polymorphism ◽  
Methylenetetrahydrofolate Reductase ◽  
Fragment Length Polymorphism ◽  
Gene Mutations ◽  
Mthfr Gene ◽  
Amplification Refractory Mutation System ◽  
Healthy Controls ◽  
Significant Difference ◽  
Mutation System ◽  
Restriction Fragment Length

Introduction. Recurrent spontaneous abortion (RSA) is a significant obstetrical complication that may occur during pregnancy. Various studies in recent years have indicated that two common mutations (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene are risk factor for RSA. This study was carried out to determine the influence of (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene mutations with RSA. Materials and Methods. A total of 139 women were included in this study: 89 women with two or more consecutive miscarriages and 50 healthy controls. Total genomic DNA was isolated from blood leukocytes. To determine the frequency of the two common C677T and A1298C MTHFR gene mutations in the patients and controls, we used two methods, amplification refractory mutation system-PCR and PCR-restriction fragment length polymorphism. Results. There is no significant difference in the prevalence of 677T/T genotype among women with RSA and healthy controls (). Also no statistically significant difference in the frequency of A1298C MTHFR gene mutation was detected between the two groups ( ). Conclusion. In conclusion, the results indicate that the Amplification Refractory Mutation System-PCR method was in complete concordance with the results obtained by standard PCR-restriction fragment length polymorphism method. The results also show no significant difference in MTHFR C677T/A1298C genotype distribution among the two groups; therefore, further studies on larger population and other genetic variants to better understand the pathobiology of RSA are needed.

scholarly journals B-vitamins, homocysteine metabolism and CVD

2004 ◽  
Vol 63 (4) ◽  
pp. 597-603 ◽  
Author(s):  
J. J. Strain ◽  
L. Dowey ◽  
M. Ward ◽  
K. Pentieva ◽  
H. McNulty
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Independent Predictor ◽  
Systemic Disease ◽  
Plasma Concentrations ◽  
Nutrient Status ◽  
Mthfr Gene ◽  
Plasma Homocysteine ◽  
B Vitamins ◽  
Vitamin B ◽  
Pathophysiological Mechanism

The present review focuses on the B-vitamins, i.e. folate, vitamin B12, vitamin B6and riboflavin, that are involved in homocysteine metabolism. Homocysteine is a S-containing amino acid and its plasma concentrations can be raised by various constitutive, genetic and lifestyle factors, by inadequate nutrient status and as a result of systemic disease and various drugs. Hyperhomocysteinaemia is a modest independent predictor of CVD and stroke, but causality and the precise pathophysiological mechanism(s) of homocysteine action remain unproven. The predominant nutritional cause of raised plasma homocysteine in most healthy populations is folate insufficiency. Vitamin B12and, to a lesser extent, vitamin B6are also effective at lowering plasma homocysteine, especially after homocysteine lowering by folic acid in those individuals presenting with raised plasma homocysteine. However, riboflavin supplementation appears to be effective at lowering plasma homocysteine only in those individuals homozygous for the T allele of the C677 T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. This gene codes for the MTHFR enzyme that produces methyltetrahydrofolate, which, in turn, is a substrate for the remethylation of homocysteine by the vitamin B12-dependent enzyme methionine synthase. Individuals with the MTHFR 677 TT genotype are genetically predisposed to elevated plasma homocysteine, and in most populations have a markedly higher risk of CVD.

scholarly journals Effect of Methylenetetrahydrofolate Reductase (MTHFR) gene mutations and oxidative stress in silent brain infarction

2021 ◽  
Author(s):  
Pınar Aslan Koşar ◽  
Muhammet Yusuf Tepebaşı ◽  
Nihat Şengeze ◽  
İlter İlhan ◽  
Halil İbrahim Büyükbayram ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Brain Infarction ◽  
Gene Mutations ◽  
White Matter Lesions ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Total Thiol ◽  
Significant Difference ◽  
Silent Brain Infarction ◽  
Fazekas Scale

Abstract Ischemic infarctions occur under the influence of genetic and environmental factors. In our study, the role of ischemia-modified albumin and thiol balance, which are new markers in determining oxidative damage together with MTHFR gene mutations and homocysteine levels, in the development of SBI was investigated. White matter lesions in the magnetic resonance imaging (MRI) results of the patients were evaluated according to the Fazekas scale and divided into groups (Grade 0, 1, 2, and 3). Homocysteine, folate, B12, IMA, total thiol, and native thiol were measured by biochemical methods. The mutations in MTHFR genes were investigated by the RT-PCR method. According to our results, a significant difference was found between the groups in age, homocysteine, folate, IMA, total thiol, and native thiol parameters (p<0.05). When we compared the groups in terms of genotypes of the C677T gene, we found a significant difference in TT genotype between grades 0/3 and 1/3 (p<0.05). We determined that homocysteine and IMA levels increased and folate levels decreased in CC/TT and CT/TT genotypes in the C677T gene (p<0.05). Considering our results, the observation of homocysteine and IMA changes at the genotype level of the MTHFR C677T gene and between the groups, and the deterioration of thiol balance between the groups suggested that these markers can be used in the diagnosis of silent brain infarction.

scholarly journals C677T polymorphism of the MTHFR gene and variant hemoglobins: a study in newborns from Salvador, Bahia, Brazil

2004 ◽  
Vol 20 (2) ◽  
pp. 529-533 ◽  
Author(s):  
Fábio David Couto ◽  
Elisângela Vitória Adorno ◽  
Joelma Figueiredo Menezes ◽  
José Pereira Moura Neto ◽  
Marco Antônio Vasconcelos Rêgo ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Methylenetetrahydrofolate Reductase ◽  
Serum Levels ◽  
Total Sample ◽  
Maternity Hospital ◽  
Mthfr Gene ◽  
C677t Polymorphism ◽  
Maternity Hospitals ◽  
Potential Risks ◽  
Total Homocysteine

The C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) is associated with an increase in total homocysteine serum levels (tHcy), described as a risk factor for cardiovascular disease. Eight hundred forty-three neonates from two different maternity hospitals, one public and another private, in Salvador, Bahia, Brazil were screened for this polymorphism by PCR and RFLP. The T-allele frequency in the total sample was 0.23, and the prevalence rates of heterozygous and homozygous carriers were 36.2% and 5.3%, respectively. The T-allele frequency differed and the T/T genotype was more prevalent at the private maternity hospital. The hemoglobin (Hb) profile was investigated by HPLC in 763 newborns. The frequency of variant Hb was higher at the public than at the private maternity hospital. The association of the C677T polymorphism and the Hb profile was investigated in 683 newborns, showing a relatively high frequency of variant Hbs and the T allele. These data could provide an important basis for further studies focusing on potential risks of vaso-occlusive events in these individuals.

scholarly journals Postgraduate Symposium The MTHFR C677T polymorphism, B-vitamins and blood pressure

2009 ◽  
Vol 69 (1) ◽  
pp. 156-165 ◽  
Author(s):  
C. P. Wilson ◽  
H. McNulty ◽  
J. M. Scott ◽  
J. J. Strain ◽  
M. Ward
Keyword(s):  
Blood Pressure ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
B Vitamins ◽  
Vitamin B ◽  
C677t Polymorphism ◽  
Mthfr Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
B Vitamin

High blood pressure (BP) and elevated homocysteine are reported as independent risk factors for CVD and stroke in particular. The main genetic determinant of homocysteine concentrations is homozygosity (TT genotype) for the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, typically found in approximately 10% of Western populations. The B-vitamins folate, vitamin B12and vitamin B6are the main nutritional determinants of homocysteine, with riboflavin more recently identified as a potent modulator specifically in individuals with the TT genotype. Although observational studies have reported associations between homocysteine and BP, B-vitamin intervention studies have shown little or no BP response despite decreases in homocysteine. Such studies, however, have not considered the MTHFR C677T polymorphism, which has been shown to be associated with BP. It has been shown for the first time that riboflavin is an important determinant of BP specifically in individuals with the TT genotype. Research generally suggests that 24 h ambulatory BP monitoring provides a more accurate measure of BP than casual measurements and its use in future studies may also provide important insights into the relationship between the MTHFR polymorphism and BP. Further research is also required to investigate the association between specific B-vitamins and BP in individuals with different MTHFR genotypes in order to confirm whether any genetic predisposition to hypertension is correctable by B-vitamin intervention. The present review will investigate the evidence linking the MTHFR C677T polymorphism to BP and the potential modulating role of B-vitamins.

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