The Effect of Methylenetetrahydrofolate Reductase C677T Common Variant on Hypertensive Risk Is Not Solely Explained by Increased Plasma Homocysteine Values

Rodrı́guez-Esparragón, Francisco; Hernández‐Perera, Octavio; Rodríguez‐Pérez, José Carlos; Anabitarte, A; Díaz-Cremades, Juan; Losada, Antonio; Fiuza, Dolores; Hernández, Enrique; Yunis, Carla; Ferrario, Carlos M.

doi:10.1081/ceh-120020391

Cited by 30 publications

(25 citation statements)

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“…Some studies have reported a gender specific association; one large population study in >3000 Japanese individuals reported that the MTHFR 677C T polymorphism was associated with a 42 % increased risk of hypertension in women but not in men (96) . In contrast, in a Spanish cohort, the TT genotype was found to be a significant predictor of hypertension in men but not in women, however, only 26 % of the sample were females (100) .…”

Section: Novel Role Of Mthfr Genotype and Blood Pressurecontrasting

confidence: 59%

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

et al. 2016

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Clinical deficiency of the B-vitamin riboflavin (vitamin B 2 ) 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 the MTHFR C677T 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 the MTHFR 677TT 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.Riboflavin: Methylenetetrahydrofolate reductase: MTHFR C677T: Blood pressure:Personalised nutrition Riboflavin (vitamin B 2 ) is a water-soluble B-vitamin defined chemically as 7,8-dimethyl-10-1′-D-ribityl isoalloxazine. It acts as a precursor for FMN and FAD (1) . Clinical riboflavin deficiency is not generally considered to be a problem in the developed world but in recent years evidence has shown that sub-optimal status may be more widespread than generally perceived based on studies reporting the functional biomarker, erythrocyte glutathione reductase activation coefficient (EGRac) generally considered as the gold standard index of status. Few international data are however available based on EGRac and reports on riboflavin status are more commonly based solely on dietary intake data. Although riboflavin is required for numerous metabolic reactions its role (in the form of FAD) as a cofactor for the folatemetabolising enzyme, methylenetetrahydrofolate reductase (MTHFR) has recently received particular attention. Homozygosity (MTHFR 677TT genotype) for a common polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide (2) , has been associated with an increased risk of CVD (3) and more recently with hypertension (4) . Emerging evidence from intervention trials supports a novel role for riboflav...

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Section: Novel Role Of Mthfr Genotype and Blood Pressurecontrasting

confidence: 59%

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

et al. 2016

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“…Our results did not reveal any gender-related differences with respect to the MTHFR C677T polymorphism and hypertension. These results are contrary to those obtained in Spain where the MTHFR TT genotype could predict the development of EH in males (Rodríguez-Esparragón et al, 2003). Our results confirm the fact that differences in ethnicity and geographical location could genetically predispose individuals to hypertension (Hong et al, 2010;Xi et al, 2014).…”

Section: Discussioncontrasting

confidence: 57%

“…Additionally, the significant association between C677T polymorphism and hypertension/ hypertension-in-pregnancy suggests that this polymorphism is an independent risk factor of hypertension (Qian et al, 2007). Consistently, studies in Asian populations (Markan et al, 2007) and Spanish subjects (Rodríguez-Esparragón et al, 2003) on the C677T polymorphism in the MTHFR gene revealed similar results. However, the involvement of the MTHFR C677T polymorphism is not consistent in all populations.…”

Section: Introductionsupporting

confidence: 71%

“…Our study therefore revealed a strong association between the T allele of the MTHFR C677T polymorphism and hypertension. These results are comparable to those obtained in populations from Spain (Rodríguez-Esparragón et al, 2003), Chinese Han (Liu et al, 2011;Li, 2012), Taichung, China (Lin et al, 2008), and Guangxi, China (Yin et al, 2012). On the contrary, our results are different from those carried out on Chinese Caucasians (Fowdar et al, 2012) and Japanese (Nakata et al, 1998), where the T allele did not predispose subjects to hypertension.…”

Section: Discussioncontrasting

confidence: 42%

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Association between the MTHFR C677T gene polymorphism and essential hypertension in South West Cameroon

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et al. 2016

Genet. Mol. Res.

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ABSTRACT. The association of the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and essential hypertension has been reported but with controversial results in diverse populations in Asia and Europe, thereby suggesting a dependency on ethnicity. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and essential hypertension in a Cameroonian population (Bantu ethnic group) of the South West Region. Analysis of anthropometric and biochemical data in hypertensive and normotensive subjects revealed that age, systolic blood pressure, diastolic blood pressure, lowdensity lipoprotein cholesterol, serum total cholesterol, and triglycerides are independent risk factors for essential hypertension. Substitution of thymine for cytosine at position 667 of the MTHFR gene was determined by polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies were found to be 7.3% CC, 58.5% CT, and 34.1% TT for hypertensive subjects compared to 90.0% CC, 10.0% CT, and 0.0% TT for normotensives. Allele frequencies were obtained as 36.6% C and 63.4% T for hypertensive subjects and 95.0% C and 5.0% T for normotensive subjects. These results reveal that the T allele predisposes individuals to hypertension. Therefore, there is an association between variants of the MTHFR gene and hypertension in Cameroonian patients from the South West region.

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“…Several other studies have failed to observe any significant relationship between the MTHFR polymorphism or homocysteine and BP (83,84) . Evidence of an independent relationship between the MTHFR polymorphism and BP has been noted (85) . While mean homocysteine concentrations were found to be significantly higher in men with hypertension, with homocysteine concentrations ‡15 mmol/l being associated with increased risk of hypertension, interestingly this outcome was not observed in men without the TT genotype but with similar homocysteine concentrations.…”

Section: Homocysteine Lowering (Via B-vitamin Supplementation) and Blmentioning

confidence: 99%

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

et al. 2009

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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 B 12 and vitamin B 6 are 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. MTHFR C677T polymorphism: B-vitamins: Homocysteine: Blood pressure CVD is one of the leading causes of death worldwide. High blood pressure or hypertension, defined as a blood pressure (BP) of > 140/90 mmHg (1) , is a major risk factor for CVD, with subjects with uncontrolled hypertension being at approximately three times greater risk of developing CVD compared with subjects who are normotensive (2) . Furthermore, hypertension is seen as the strongest predictor of stroke risk (3) . The relationship between BP and CVD risk is continuous across a wide range of values, with evidence indicating that the association with CVD mortality is apparent down to BP levels of 115/75 mmHg (4) . BP reduction, through the use of antihypertensive therapy, has been shown to reduce cardiovascular events, in particular stroke (5) , and it can effectively reduce the recurrence of stroke even in individuals with normal BP values (6) . The prevalence of hypertension is estimated to be as high as 40% in the UK population but its detection and management are often suboptimal (7) . The exact pathophysiology of hypertension is unclear but in the majority of instances no single cause is identifiable, with various factors such as age, obesity, diet, physical activity and genetic factors being thought to play a role.Evidence has accumulated in recent years to suggest that elevated homocystein...

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The Effect of Methylenetetrahydrofolate Reductase C677T Common Variant on Hypertensive Risk Is Not Solely Explained by Increased Plasma Homocysteine Values

Cited by 30 publications

References 27 publications

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

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

Association between the MTHFR C677T gene polymorphism and essential hypertension in South West Cameroon

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

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