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.

scholarly journals Effect of riboflavin supplementation on blood pressure and possible effect modification by the MTHFR C677T polymorphism: a randomised trial in rural Gambia

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1034
Author(s):  
Modou Jobe ◽  
Mary Ward ◽  
Bakary Sonko ◽  
Abdul Khalie Muhammad ◽  
Ebrima Danso ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Large Scale ◽  
Methylenetetrahydrofolate Reductase ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Phenotypic Effect ◽  
Riboflavin Deficiency ◽  
Mthfr C677t Polymorphism

Introduction: Emerging evidence links a functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene (rs1801133) with hypertension in adults. This variant reduces the affinity of MTHFR for its cofactor flavin-adenine dinucleotide (FAD) which is derived from riboflavin. Previous work has demonstrated a blood pressure (BP)-lowering effect of riboflavin in Irish adults with the MTHFR 677TT variant. We hypothesize that the almost-universal severe riboflavin deficiency seen in rural Gambia mimics the BP phenotypic effect of the TT variant and exacerbate the effect of the CT variant. We will test this in a randomised, placebo-controlled trial, whether intervention with riboflavin can decrease BP in adults in rural Gambia. Methods: This is a phase 2 recall-by-genotype randomised single-blind placebo-controlled riboflavin supplementation trial. We will use the Keneba biobank to recruit approximately 102 individuals aged between 18-70, previously genotyped for the MTHFR C677T polymorphism and identified as carrying the T allele; these individuals will be age- and sex-matched to a similar number of homozygotes for the C allele. The participants will be randomised to a 16-week supplementation trial of 5 mg/day riboflavin or placebo, supplied every 14 days. The primary outcome, BP, will be measured at baseline and at weeks 8 and 16. Blood samples, collected at baseline and week 16, will be analysed for riboflavin, homocysteine, red cell folate, cobalamin (vitamin B12) and pyridoxine (vitamin B6). Discussion: The study will evaluate the role of riboflavin supplementation in BP control within a population with high levels of riboflavin deficiency and will test a possible gene-nutrient interaction with the MTHFR C677T polymorphism. If improvements in BP are observed in this study, and proven in subsequent large-scale interventions, riboflavin could offer a cost-effective, safe and accessible option for the  prevention and control of hypertension in this population. Trial registration: ClinicalTrials.gov Identifier NCT03151096. Registered on 12 May 2017.

scholarly journals Plasma Homocysteine Level And C677T Polymorphism In MTHFR Gene In Patients With Acute Coronary Syndrome

2015 ◽  
Vol 8 (1) ◽  
pp. 46-51
Author(s):  
Andrey V. Grek ◽  
Lyudmyla N. Prystupa ◽  
Tatiana V. Sytnik
Keyword(s):  
Acute Coronary Syndrome ◽  
Endothelial Dysfunction ◽  
Homocysteine Level ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Control Group ◽  
C677t Polymorphism ◽  
Mthfr Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Coronary Syndrome

SummaryCardiovascular diseases (CVD) of atherosclerotic origin and accompanying complications are a major cause of mortality in the world and Ukraine, in particular. Endothelial dysfunction is the key cause of atherosclerosis and atherothrombosis. One of the causes of endothelial dysfunction is hyperhomocysteinemia that may occur on the background of MTHFR (methylenetetrahydrofolate reductase) mutation.Thus, the goal of the study was to investigate the interrelation between homocysteine (Hc) level and MTHFR polymorphism in patients with acute coronary syndrome (ACS).161 patients with ischemic heart disease and ACS have been examined. The control group comprised 87 healthy individuals. Homocysteine level was the highest in the patients having ACS with ST-segment elevation and complicated course, and was 1.8 times higher than Hc level in the control group. The patients with the most severe ACS course comprised 27 % of homozygotes for the major allele C and 41 % of homozygotes for the minor allele T. Comparing the distribution of MTHFR gene C677T polymorphism in patients with ACS that were stratified by plasma Hc level, we observed a statistically significant association, P < 0.030 by chi-square test. We confirmed that these patients had a high T/T genotype frequency of MTHFR C677T polymorphism. The obtained data proved the association of T/T genotype of MTHFR C677T polymorphism with increased Hc level as well as ACS severity.

Nutritional Factors, Homocysteine and C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene in Algerian Subjects with Cardiovascular Disease

Pteridines ◽  
2012 ◽  
Vol 23 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Zahira Houcher ◽  
Bakhouche Houcher ◽  
Abderrezak Touabti ◽  
Samia Begag ◽  
Yonca Egin ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Total Cholesterol ◽  
Methylenetetrahydrofolate Reductase ◽  
Elevated Serum ◽  
Vitamin B ◽  
C677t Polymorphism ◽  
Mthfr Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Plasma Folate ◽  
Plasma Thcy

Abstract The C677T variant of methylenetetrahydrofolate reductase (MTHFR), a key enzyme in the remethylation of homocysteine (HCY) to methionine, is a frequent genetic cause of moderate hyperhomocysteinemia (HHCY) among individuals with cardiovascular disease (CVD), and particularly when combined with other factors such as hyperlipidaemia. However, in Algeria the influence of nutrient-gene interactions is not known. The aim of the present study was to explore the influence of age and gender, together with folate status, on the association between the C677T MTHFR polymorphism and plasma total HCY (tHCY) concentrations. This research was carried out as a prospective study on 98 patients hospitalized in the Cardiology Section, University of Sétif, Algeria. Mean age of participants was 57 y (range 20-96 y).The genetic analysis of the MTHFR C677T polymorphism was performed by real-time polymerase chain reaction (PCR) performed on Light Cycler in borosilicate capillaries with MTHFR 677CT polymorphism detection kit. The concentrations of tHCY, folic acid vitamin B12 levels were determined using a competitive immunoassay on the IMMULITE 1000 Analyzers. Plasma total cholesterol, triglycerides, glucose, creatinine and urea concentrations were measured by colorimetric methods. Assays were conducted according to the manufacturers' instructions. Plasma tHCY was significantly higher in the patients with CVD, and HHCY was associated with the presence of mildly elevated serum urea and creatinine (p <0.05). MTHFR gene mutation does not seem to be associated with elevation of plasma tHCY in the studied patients and this lack of correlation could be influenced by the higher folate concentrations in our study. CVD patients with 677CT/TT genotypes had a higher concentration of total cholesterol than those with 677CC genotype (p <0.05). Although, the presence of 677T variant together with hypofolatemia (<15.4 ng/ml) had a more detrimental effect on the level of total cholesterol (p <0.05). Folatemia and vitamin B12 were much higher in 677CC genotype compared to 677CT/TT genotype in CVD subjects without hyperlipidemia (p <0.05). However in patients with hyperlipidemia these values became lower also with 677CC genotype. In conclusion, hyperlipidemia affects the levels of plasma folate and vitamin B12 concentrations independent of mutated MTHFR genotype. The effect of 677T variant on total cholesterol, folate and vitamin B12 concentrations may relate to possible adverse effects of elevated tHCY on lipid profiles and on plasma folate and vitamin B12.

scholarly journals Methylenetetrahydrofolate reductase gene C677T polymorphism and risk of alcohol dependence

2020 ◽  
Author(s):  
Vandana Rai ◽  
Pradeep Kumar
Keyword(s):  
Alcohol Dependence ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Random Effects Model ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Reductase Gene ◽  
Methylenetetrahydrofolate Reductase Gene

AbstractAlcohol dependence is a complex neuropsychiatric disorder. Numerous studies investigated association between MTHFR gene C677T polymorphism and alcohol dependence (AD), but the results of this association remain conflicting. Accordingly, authors conducted a meta-analysis to further investigate such an association. PubMed, Elsevier Science Direct and Springer Link databases were searched for studies on the association between the MTHFR C677T polymorphism and AD. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed- or random-effects model. Statistical analysis was performed with the software program MetaAnayst and MIX.A total of 11 articles were identified through a search of electronic databases, up to February 28, 2020. The results of the present meta-analysis did not show any association between MTHFR C677T polymorphisms and AD risk (for T vs. C: OR = 1.04, 95% CI = 0.88-1.24; CT vs. CC: OR=1.02, 95%CI= 0.62-1.68; for TT + CT vs. CC: OR = 1.10, 95% CI = 0.94-1.29; for TT vs. CC: OR = 1.01, 95% CI = 0.66-1.51; for TT vs. CT + CC: OR = 0.97, 95% CI = 0.66-1.40). Results of subgroup analysis showed no significant association between MTHFR C677T polymorphism with AD in Asian as well as in Caucasian population. In conclusion, C677T polymorphism is not a risk factor for alcohol dependence.

Roles of Methylenetetrahydrofolate Reductase C677T Polymorphism in Repeated Pregnancy Loss

2005 ◽  
Vol 11 (3) ◽  
pp. 343-345 ◽  
Author(s):  
Viroj Wiwanitkit
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Risk Estimation ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
C677t Polymorphism ◽  
Case Control Studies ◽  
Clinical Role ◽  
Mthfr C677t Polymorphism ◽  
Increased Risk ◽  
Considerable Controversy

Congenital thrombophilia in repeated pregnancy lost (RPL) has been noted for years. Methylenetetrahydrofolate reductase (MTHFR) gene is an interesting gene, mentioned for its possible roles in RPL. There is considerable controversy regarding the clinical role of MTHFR C677T polymorphism as a risk factor of RPL. Here, a summative analysis is performed on the recent previous reports on the MTHFR C677T and its correlation to RPL. The metanalysis was performed to assess the correlation between the pattern of MTHFR C677T polymorphism and RPL. From available eight case-control studies, 752 patients and 625 controls are evaluated. The overall frequencies of 4G allele for the patients and controls are 31.5 and 33.5, respectively. According to this study, 53.1% of subjects with T allele have RLP while 55.3% of subjects without T allele have RLP. From overall risk estimation, the subjects with T alleles have 0.96 times lower risk to RLP. According to this analysis, the pattern of MTHFR C677T polymorphism might not represent a useful marker of increased risk for RPL. In addition, there was no association between pattern of MTHFR C677T polymorphism and ethnicity of the patients in this study.

scholarly journals Relation between Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Migraine Susceptibility

2019 ◽  
Author(s):  
Vandana Rai ◽  
Pradeep Kumar
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Association Studies ◽  
Meta Analysis ◽  
Asian Population ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Genetic Models ◽  
C677t Polymorphism ◽  
Case Control Studies ◽  
Mthfr C677t Polymorphism

AbstractMigraine is a neurological disorder which impairs the patient’s quality of life. Several association studies investigating the association between MTHFR gene C677T and A1298C polymorphisms and susceptibility to migraine were published. But the results were conflicting, so authors performed a meta-analysis of published case control studies. Four databases were searched for suitable studies up to December, 2018. Odds ratios (OR) with 95% confidence intervals (CI) was calculated adopting additive, homozygote, co-dominant, dominant, and recessive genetic models.Results of MTHFR C677T polymorphism studies meta-analysis showed significant association with migraine risk using allele contrast, homozygote, dominant and recessive genetic models (T vs. C: OR = 1.18, 95%CI = 1.00-1.26, p= 0.05; TT vs. CC: OR = 1.24, 95%CI = 1.0-1.5, p= 0.04; CT vs. CC: OR = 1.08, 95%CI = 0.97-1.07, p= 0.25; TT+CT vs. CC: OR = 1.15, 95%CI = 1.0-1.29, p= 0.04; TT vs. CT +CC: OR = 1.97, 95%CI = 1.28-3.42, p= 0.002). However, results of MTHFR A1298 polymorphism studies meta-analysis did not show any association with migraine. Subgroup analysis based on ethnicity and migraine types i. e migraine with aura (MA) and without aura (MO) were also performed. Results of present meta-analysis indicate overall association between MTHFR C677T polymorphism with migraine in total 24 studies, in Asian population and in MA cases but did not show any association with Caucasian population and MO cases.

scholarly journals Association between methylenetetrahydrofolate reductase gene C677T polymorphism and susceptibility to polycystic ovary syndrome

2020 ◽  
Author(s):  
Vandana Rai ◽  
Pradeep Kumar
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Case Control ◽  
Mthfr Gene ◽  
C677t Polymorphism ◽  
Case Control Studies ◽  
Ovary Syndrome ◽  
Mthfr C677t Polymorphism

AbstractPolycystic ovary syndrome (PCOS) is the most common form of endocrinopathy of women. Several studies have investigated the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with PCOS risk but the results are contradictory. So, the aim of the present study was to carry out a meta-analysis of a published case control studies to find out exact association between MTHFR gene C677T polymorphism and PCOS susceptibility. Pubmed, Springer link, Science Direct and Google Scholar databases were searched for case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) was used as association measure and meta-analysis was performed using MIX and MetaAnalyst programs.Meta-analysis of 24 studies showed strong significant association between C677T polymorphism and PCOS risk (for T vs. C: OR= 1.18, 95% CI=1.01-1.38, p=0.03; for TT vs. CC: OR= 1.37, 95% CI=1.0-1.89, p= 0.045; for TT + CT vs. CC: OR= 1.31, 95% CI= 1.07-1.62, p= 0.008; for CT vs. CC: OR= 1.31, 95% CI= 1.04-1.62, p= 0.01 and for TT vs. CT + CC: OR= 1.10, 95% CI= 0.82-1.47, p= 0.04). In subgroup analysis, MTHFR C677T polymorphism is significantly associated with PCOS risk with Asian individuallas but in Caucasian population MTHFR C677T polymorphism was not significantly associated with PCOS risk. In conclusion, C677T polymorphism is a risk factor for PCOS.

scholarly journals Methylenetetrahydrofolate reductase C677T polymorphism and toxicity to 5-FU-based chemotherapy in colorectal cancer

2020 ◽  
Vol 19 (1) ◽  
pp. 209-213
Author(s):  
Yong-lian Zhang ◽  
Xiong-wei Xie
Keyword(s):  
Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Direct Sequencing ◽  
Skin Toxicity ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Mthfr Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
C677t Mutation ◽  
Hematopoietic Toxicity

Purpose: To investigate the toxicity of methylenetetrahydrofolate reductase (MTHFR) polymorphism in colorectal cancer patients treated with 5-fluorouracil (5-FU).Methods: A total of 105 patients with colorectal cancer who underwent 5-FU therapy were included in this study. MTHFR C677T polymorphisms were determined using direct sequencing. Physical examination and the results of blood and urine tests were used to evaluate the toxicities, including gastrointestinal toxicity, hematopoietic toxicity, hair-skin toxicity and hand-foot syndrome.Results: In 90.5 % of all patients, 5-FU toxicity was observed. With regard to MTHFR C677T mutation, 45.7 % heterozygote mutants and 19.0 % homozygote mutants were observed. MTHFR C677T polymorphism was statistically related to 5-FU toxicity (p = 0.000). In addition, MTHFR C677T mutation was closely related to hematopoietic toxicity (p = 0.005).Conclusion: MTHFR C677T can be used for the prediction of 5-FU toxicity, and can also predict hematopoietic toxicity in patients with colorectal cancer. Keywords: MTHFR genes, Polymorphism, Colorectal cancer, Biomarker, Toxicity

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