P3566Ambulatory blood pressure response to riboflavin supplementation in adults with the C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Ward ◽  
C F Hughes ◽  
A Mc Mahon ◽  
M Rooney ◽  
J J Strain ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Blood Pressure Response ◽  
P Value ◽  
C677t Polymorphism ◽  
Night Time ◽  
Reliable Assessment ◽  
Increased Risk ◽  
Clinical Research Facility ◽  
To Receive ◽  
Riboflavin Status

Abstract Background Epidemiological evidence suggests that the C677T polymorphism in the folate metabolising enzyme MTHFR is associated with a 24–87% increased risk of hypertension. Riboflavin (a cofactor for MTHFR) can modify this phenotype, as demonstrated in a series of RCTs, at this centre. ABPM measures BP over 24hrs and provides a more reliable assessment of an individual's BP compared to clinic BP. Aim To investigate the effect of riboflavin supplementation on BP (by ABPM) in adults with the MTHFR 677TT genotype. Methods Adults (n=3462) were recruited and screened for the MTHFRTT genotype and those eligible (n=81), were stratified by baseline SBP and randomised to receive riboflavin (10mg/day/16weeks) or placebo. Riboflavin status was measured using the erythrocyte glutathione reductase activation coefficient (EGRac) assay and clinic and ABPM were measured in accordance with clinical guidelines. Results Mean 24hr, daytime and night-time SBP was 6mmHg higher (p<0.05) in adults with the TT v CC genotype. BP response to riboflavin was strongly dependent on baseline BP. In participants with a baseline SBP≥125mmHg, riboflavin resulted in a significant BP lowering in daytime SBP (Table). Day-time SBP response to riboflavin Treatment Placebo P-value Age 48.6 (11.3) 47.8 (12.0) 0.823 Male n (%) 17 (73.9) 12 (46.2) 0.093 BMI 28.8 (3.8) 27.2 (3.1) 0.131 Riboflavin status (EGRac)†   Pre 1.33 (1.28–1.38) 1.29 (1.24–1.34)   Post 1.20 (1.14–1.25) 1.31 (1.25–1.36) <0.001   Change −0.12 0.02 Daytime BP (mmHg)‡   Pre 137.1 (132.7–141.3) 134.7 (130.3–139.1)   Post 133.0 (128.9–138.1) 134.8 (130.6–139.1) 0.036   Change −3.8 −0.2 ANCOVA, adjusting for sex. †Higher EGRac values indicate lower riboflavin status; ‡mean of participant daytime/awake hrs personalised for each participant. Conclusion This is the first study to show, using ABPM, that riboflavin supplementation, targeted at adults with the MTHFR 677TT genotype, results in significant lowering of mean, day and night BP. Given the frequency of this genotype worldwide (approximately 10%, but as high as 30% in some populations) these findings could offer a personalised approach for BP management in at-risk sub-populations. Acknowledgement/Funding This work was supported by DSM Nutritional Products, Ltd and Wellcome Trust-Wolfston Northern Ireland Clinical Research Facility are acknowledged

scholarly journals Riboflavin status, MTHFR genotype and blood pressure: current evidence and implications for personalised nutrition

2016 ◽  
Vol 75 (3) ◽  
pp. 405-414 ◽  
Author(s):  
E. McAuley ◽  
H. McNulty ◽  
C. Hughes ◽  
J. J. Strain ◽  
M. Ward
Keyword(s):  
Blood Pressure ◽  
Methylenetetrahydrofolate Reductase ◽  
Current Evidence ◽  
C677t Polymorphism ◽  
Personalised Nutrition ◽  
Increased Risk ◽  
Randomised Controlled ◽  
The Uk ◽  
Riboflavin Status

Clinical deficiency of the B-vitamin riboflavin (vitamin B2) is largely confined to developing countries; however accumulating evidence indicates that suboptimal riboflavin status is a widespread problem across the developed world. Few international data are available on riboflavin status as measured by the functional biomarker, erythrocyte glutathione reductase activation coefficient, considered to be the gold standard index. One important role of riboflavin in the form of flavin dinucleotide is as a co-factor for the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the common C677T polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide, has been associated with an increased risk of CVD, and more recently with hypertension. This review will explore available studies reporting riboflavin status worldwide, the interaction of riboflavin with theMTHFRC677T polymorphism and the potential role of riboflavin in personalised nutrition. Evidence is accumulating for a novel role of riboflavin as an important modulator of blood pressure (BP) specifically in individuals with theMTHFR677TT genotype, with results from a number of recent randomised controlled trials demonstrating that riboflavin supplementation can significantly reduce systolic BP by 5–13 mmHg in these genetically at risk adults. Studies are however required to investigate the BP-lowering effect of riboflavin in different populations and in response to doses higher than 1·6 mg/d. Furthermore, work focusing on the translation of this research to health professionals and patients is also required.

Methylenetetrahydrofolate reductase C677T polymorphism is associated with increased risk of coronary artery disease in young South African Indians

Gene ◽  
2015 ◽  
Vol 571 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Prithiksha Ramkaran ◽  
Alisa Phulukdaree ◽  
Sajidah Khan ◽  
Devapregasan Moodley ◽  
Anil A. Chuturgoon
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
South African ◽  
Methylenetetrahydrofolate Reductase ◽  
C677t Polymorphism ◽  
Increased Risk ◽  
Artery Disease

scholarly journals Association of MTHFR C677T polymorphism with severity and localization of chronic atrophic gastritis: a case control study

2020 ◽  
Author(s):  
Siya Kong ◽  
Feng Ye ◽  
Yini Dang ◽  
Yifei Hua ◽  
Guoxin Zhang
Keyword(s):  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Methylenetetrahydrofolate Reductase ◽  
Predictive Marker ◽  
Staging System ◽  
Mthfr C677t ◽  
Categorical Variables ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Increased Risk

Abstract Background Previous reports indicate that the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism plays a role in gastric cancer. However, whether it influences the development and progression of atrophic gastritis remains unclear. We aim to determine the possible association between the MTHFR 677C > T polymorphism and the severity of atrophic gastritis. Methods A total 128 patients with atrophic gastritis were included in the study. The presence and severity of gastric atrophy was assessed by histology using OLGA and OLGIM Gastritis Staging System. MTHFR 677C > T genotyping was performed by digital fluorescence molecular hybridization. Categorical variables were analyzed by percentages using the χ2 test. Results In this study, the TT genotype was significantly more frequent among patients aged ≤ 44 years (age ≤ 44 years vs. >44 years, P = 0.039). Patients with the TT genotype showed a higher ratio of incisura with atrophy or intestinal metaplasia (TT vs. CC + CT, P = 0.02). Furthermore, the TT genotype was associated with more severe lesions compared with the CC + CT genotypes (TT vs. CC + CT for atrophy: odds ratio [OR] = 2.18, P = 0.07; for intestinal metaplasia: OR = 3.39, P = 0.02; for moderate-to-severe lesions: OR = 3.84, P = 0.02). OLGA and OLGIM stages III-IV were observed more frequently in patients with the TT genotype compared with the CC + CT genotypes (for OLGA: OR = 3.98, P = 0.004; for OLGIM: OR = 2.45, P = 0.04). Conclusions The MTHFR 677C > T TT genotype showed an increased risk of moderate-to-severe lesions by OLGA and OLGIM stages, and these results suggest that the MTHFR C677T polymorphism may serve as a predictive marker for precancerous gastric lesions, especially in patients aged ≤ 44 years.

scholarly journals Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4562
Author(s):  
Shanel Raghubeer ◽  
Tandi E. Matsha
Keyword(s):  
Carbon Cycle ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
C677t Polymorphism ◽  
Cardiovascular Risks ◽  
Mthfr Polymorphism ◽  
Dna And Rna ◽  
Inflammatory Conditions ◽  
Increased Risk ◽  
The One

The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the MTHFR gene, especially C677T, have been associated with various diseases, including cardiovascular diseases (CVDs), cancer, inflammatory conditions, diabetes, and vascular disorders. The C677T MTHFR polymorphism is thought to be the most common cause of elevated Hcy levels, which is considered an independent risk factor for CVD. This polymorphism results in an amino acid change from alanine to valine, which prevents optimal functioning of the enzyme at temperatures above 37 °C. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and increased risk for CVD. There is much evidence in favour of this association, while several studies have concluded that the polymorphism cannot be used to predict CVD development or progression. This review discusses current research regarding the C677T polymorphism and its relationship with CVD, inflammation, diabetes, and epigenetic regulation and compares the evidence provided for and against the association with CVD.

scholarly journals Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mary Ward ◽  
Catherine F. Hughes ◽  
J. J. Strain ◽  
Rosie Reilly ◽  
Conal Cunningham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Risk ◽  
Antihypertensive Treatment ◽  
Methylenetetrahydrofolate Reductase ◽  
Randomised Trial ◽  
Population Based ◽  
Nutrition Survey ◽  
Increased Risk ◽  
The Impact ◽  
Riboflavin Status

Abstract Background Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. Methods Observational data on 6076 adults of 18–102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008–2012 using standardised methods. Results The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34–6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). Conclusions The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.

MTHFR 677CC/1298CC Genotypes Are Highly Associated with Chronic Myelogenous Leukemia: A Case-Control Study in Korea.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4533-4533
Author(s):  
Hee Won Moon ◽  
Tae Young Kim ◽  
Bo Ra Oh ◽  
Hyun Chung Min ◽  
Han Ik Cho ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Protective Role ◽  
Myelogenous Leukemia ◽  
P Value ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Mthfr Polymorphism ◽  
Increased Risk ◽  
Healthy Control

Abstract Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism and DNA methylation. Studies on MTHFR polymorphism in leukemia have largely focused on the protective role of MTHFR polymorphism in ALL. We evaluated the C677T and A1298C polymorphisms using the TaqMan® allelic discrimination assay in various malignancies. The study population included 115 subjects with CML, 200 with AML, 196 with MM and 434 healthy control subjects. The frequency of 1298 CC was statistically significantly higher in subjects with CML than that of the controls (OR = 5.12, 95% CI: 1.75–14.9, P value =.003). Of note, the frequencies of 677CC/1298CC genotype was statistically significantly higher in subjects with CML, AML and MM than that of the controls (OR = 8.8, 3.5, 3.83, P value =.002, 0.036, 0.023, respectively). Our results demonstrate that the MTHFR 1298CC homozygote variant is strongly associated with an increased risk of CML, while MTHFR C677T does not significantly affect the risk of CML. Moreover, we demonstrated that MTHFR 677CC and 1298CC genotype might have combined effect on risk of CML, AML and MM and it is inferred that the A1298C may play a different role in carcinogenesis, depending on the types of organs involved, the types of disease entities and the genotype of C677T.

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 Intakes and status of riboflavin in a representative sample of Irish adults aged 18–90 years screened for MTHFR C677T polymorphism

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Emma O'Sullivan ◽  
Laura Kehoe ◽  
Janette Walton ◽  
Helene McNulty ◽  
Mary Ward ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dietary Intake ◽  
Representative Sample ◽  
Functional Assay ◽  
C677t Polymorphism ◽  
Increased Risk ◽  
Significant Difference ◽  
Nationally Representative ◽  
The Impact ◽  
Riboflavin Status

AbstractMeta-analyses of epidemiological data report that adults who carry a common polymorphism, the MTHFR 677C→T, in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) have a 40% increased risk of CVD and an 87% increased risk of hypertension. Riboflavin (vitamin B2), in its co-enzymatic form flavin adenine nucleotide (FAD), is required as a co-factor by MTHFR and previous trials in hypertensive patients have shown a blood pressure lowering response to riboflavin supplementation that is specific to individuals homozygous for this polymorphism (TT genotype). Low folate status is commonly reported in adults with the TT genotype however the effect of this genetic variant on riboflavin status has not previously been investigated. The aim of this study, therefore, was to investigate dietary intake and biomarker status of riboflavin by MTHFR genotype in Irish adults using data from the National Adult Nutrition Survey (2008–2010) (www.iuna.net).A 4-day semi-weighed food record was used to collect food and beverage intake data from a representative sample of 1500 Irish adults (18–90 years). Dietary intake data were analysed using WISP© based on UK food composition tables (modified to include recipes of composite dishes, nutritional supplements, fortified foods and generic Irish foods that were commonly consumed). Usual intakes were calculated via the NCI-method using SAS© Enterprise Guide. Blood samples (n = 1126) were collected by venepuncture by a trained professional and were processed and analysed using standard operating procedures. Biomarker status of riboflavin was determined by erthyrocyte gluthathione reductase activation coefficient (EGRac), a functional assay that measures the activity of the enzyme glutathione reductase before and after in vitro activation with its prosthetic group FAD; a lower value indicates better status.It was found that 12% of the population had the TT genotype. As expected, there was no significant difference in riboflavin intake across the genotype (CC, CT or TT) groups. Similarly, no significant genotype differences in riboflavin status (EGRac) were observed (1.36 vs 1.37 vs 1.38 respectively). Overall, 61% of the total population had EGRac values > 1.3, indicative of low/deficient status with no significant difference observed between the genotype groups (60%,61% and 61%, respectively).These data suggest that riboflavin status is not influenced by the C677T polymorphism in MTHFR in this cohort of nationally representative Irish adults. Further research is needed to see the impact of riboflavin status on blood pressure across the genotype groups in this nationally representative cohort of Irish adults.

scholarly journals A Study on MTHFR C677T Gene Polymorphism and Alcohol Dependence among Meiteis of Manipur, India

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Huidrom Suraj Singh ◽  
Kabita Salam ◽  
Kallur Nava Saraswathy
Keyword(s):  
Alcohol Dependence ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Allelic Frequency ◽  
Control Group ◽  
Drinking Patterns ◽  
C677t Polymorphism ◽  
Increased Risk ◽  
Hardy Weinberg Equilibrium ◽  
Alcohol Dependent

Chronic alcohol consumption is reported to be associated with increase in plasma homocysteine levels which is further influenced by the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD) cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls were unrelated up to 1st cousin. Among the control group, different drinking patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and moderate drinkers (MDs) are included. Both the groups were found to be in Hardy-Weinberg equilibrium (P>0.05). Genotypic and allelic frequency distribution of MTHFR C677T polymorphism did not differ significantly between AD cases and controls (P>0.05). However, individuals carrying mutant (T) allele show more than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41–5.01, P>0.05). In conclusion, MTHFR C677T polymorphism is not found to be risk marker for AD in present studied population. However, higher prevalence of the mutant T allele may exacerbate deleterious health risk in future especially among alcohol drinkers.

scholarly journals Association of MTHFR C677T polymorphism with severity and localization of chronic atrophic gastritis patients without Helicobacter pylori infection : a case control study

2020 ◽  
Author(s):  
Siya Kong ◽  
Feng Ye ◽  
Yini Dang ◽  
Yifei Hua ◽  
Guoxin Zhang
Keyword(s):  
Helicobacter Pylori ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Methylenetetrahydrofolate Reductase ◽  
Predictive Marker ◽  
Mthfr C677t ◽  
Categorical Variables ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Increased Risk

Abstract Background: Previous reports indicate that the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism plays a role in gastric cancer. However, whether it influences the development and progression of atrophic gastritis remains unclear. We aimed to determine the possible association between the MTHFR 677C>T polymorphism and the severity of atrophic gastritis.Methods: A total 128 patients without Helicobacter pylori infection were included in the study. The presence and severity of gastric atrophy was assessed by histology using OLGA and OLGIM Gastritis Staging System. MTHFR 677C>T genotyping was performed by digital fluorescence molecular hybridization. Categorical variables were analyzed by percentages using the χ2 test.Results: In this study, the TT genotype was significantly more frequent among Helicobacter pylori-negative patients aged ≤44 years (age ≤44 years vs. >44 years, P=0.039). Patients with the TT genotype showed a higher ratio of incisura with atrophy or intestinal metaplasia (TT vs. CC+CT, P=0.02). Furthermore, the TT genotype was associated with more severe lesions compared with the CC+CT genotypes (TT vs. CC+CT for atrophy: P=0.07; for intestinal metaplasia: P=0.01; for moderate-to-severe lesions: P=0.01). OLGA and OLGIM stages III-IV were observed more frequently in patients with the TT genotype compared with the CC+CT genotypes (for OLGA: P=0.003; for OLGIM: P=0.036).Conclusions: The MTHFR 677C>T TT genotype showed an increased risk of moderate-to-severe lesions by OLGA and OLGIM stages, and these results suggest that the MTHFR C677T polymorphism may serve as a predictive marker for precancerous gastric lesions, especially in Helicobacter pylori-negative patients aged ≤44 years.

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