The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor

Jiang, Shanqun; Hsu, Yi‐Hsiang; Xu, Xin; Huang, Xing; Chen, Changzhong; Niu, Tianhua; Zhang, Yan; Peng, Shaojie; Xu, Xiping

doi:10.1016/j.thromres.2004.04.005

Cited by 24 publications

(22 citation statements)

References 36 publications

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“…Generally consistent with these findings from genomewide association studies, there is a growing body of evidence from observational studies to support a specific association between the 677C T polymorphism in the MTHFR gene and BP variation (91)(92)(93)(94) . As the evidence has accumulated numerous meta-analysis were conducted, all reporting significant associations of the MTHFR 677C…”

Section: Novel Role Of Mthfr Genotype and Blood Pressuresupporting

confidence: 57%

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 Pressuresupporting

confidence: 57%

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

et al. 2016

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“…These results were consistent with previous clinical and animal studies (24,25). Hcy levels have been reported to be higher in patients with essential hypertension compared with normotensive subjects, with higher levels of Hcy being associated with an increased risk of hypertension (26). Furthermore, increased SBP/DBP returned to control values when Hcy levels were normalized following the discontinuation of Hcy-elevating treatment (27).…”

Section: Discussionsupporting

confidence: 91%

Vascular protective effects of Astragalus membranaceus and its main constituents in rats with chronic hyperhomocysteinemia

Qiu

Zhang

Lian

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Hyperhomocysteinemia (HHcy) is an important factor in cardiovascular disease. However, is currently no cure available in western medicine for HHcy-evoked cardiovascular disease. The present study explored the vascular protective effects of Astragalus membranaceus (AM), a traditional Chinese medicine. Rats with HHcy were induced by feeding high-methionine diets and treated with total extract of AM (TEA) and its constituents, including Astragalus saponins (ASP), Astragalus total flavonoids (ATF) and Astragalus polysaccharides (APS). Examination of the rats indicated that TEA and ASP controlled blood pressure and ameliorated HHcy-induced impairment of endothelium-dependent vasorelaxation by increasing the nitric oxide content and nitric oxide synthase activity of the abdominal aorta. Furthermore, they decreased the accumulation of hydrogen peroxide and superoxide anion, and attenuated the inhibition of superoxide dismutase and catalase activities in rats with HHcy. Additionally, TEA and ASP attenuated the HHcy-induced increases of matrix metalloproteinase (MMP)-2 and -9 concentrations. However, similar effects were not observed for ATF and APS. In conclusion, TEA and ASP are beneficial to vascular disease, and their effects may be attributed to protective actions against oxidation, activity of the MMPs and endothelial dysfunction.

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“…with high genetic complexity, as indicated by multiple independent associations with BP and renal phenotypes in the human population (Kato et al 2000;Jiang et al 2004;Zhang et al 2005;Levy et al 2009;Newton-Cheh et al 2009a,b;Chen et al 2010;Tomaszewski et al 2010;Johnson et al 2011;Liu et al 2011;Fung et al 2012). By combining rat phenotype data ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Strains were tested for eight cardiovascular disease (CVD)-associated phenotypes following a 10-d high-salt challenge (see Methods and Table 1). Because BP and renal phenotypes are most commonly reported in human studies (Kato et al 2000;Jiang et al 2004;Zhang et al 2005;Levy et al 2009;Newton-Cheh et al 2009a,b;Chen et al 2010;Tomaszewski et al 2010;Johnson et al 2011;Liu et al 2011;Fung et al 2012), we focused specifically below on the (+), (À), and (=) effects of mutant alleles on BP and urinary protein excretion (a commonly used index for renal damage).…”

Section: Strain Generation and Phenotyping Strategymentioning

confidence: 99%

“…We phenotyped rats with mutations in the Agtrap-Plod1 locus, which has been associated with blood pressure (BP) or renal disease in 11 human studies (Supplemental Table 1; Kato et al 2000;Jiang et al 2004;Zhang et al 2005;Levy et al 2009;Newton-Cheh et al 2009a,b;Chen et al 2010;Tomaszewski et al 2010;Johnson et al 2011;Liu et al 2011;Fung et al 2012), yet the genetic mechanism(s) underlying this locus were completely unknown. We used a recent technological advancement-zinc-finger nuclease (ZFN) mutagenesis (Geurts et al 2009)-to introduce damaged alleles into each of the six Agtrap-Plod1 genes (Agtrap, Mthfr, Clcn6, Nppa, Nppb, and Plod1) in a rodent model of genetic hypertension, the SS (SS/JrHsdMcwi) rat.…”

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confidence: 99%

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Identifying multiple causative genes at a single GWAS locus

et al. 2013

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Genome-wide association studies (GWAS) are useful for nominating candidate genes, but typically are unable to establish disease causality or differentiate between the effects of variants in linkage disequilibrium (LD). Additionally, some GWAS loci might contain multiple causative variants or genes that contribute to the overall disease susceptibility at a single locus. However, the majority of current GWAS lack the statistical power to test whether multiple causative genes underlie the same locus, prompting us to adopt an alternative approach to testing multiple GWAS genes empirically. We used gene targeting in a disease-susceptible rat model of genetic hypertension to test all six genes at the Agtrap-Plod1 locus (Agtrap, Mthfr, Clcn6, Nppa, Nppb, and Plod1) for blood pressure (BP) and renal phenotypes. This revealed that the majority of genes at this locus (five out of six) can impact hypertension by modifying BP and renal phenotypes. Mutations of Nppa, Plod1, and Mthfr increased disease susceptibility, whereas Agtrap and Clcn6 mutations decreased hypertension risk. Reanalysis of the human AGTRAP-PLOD1 locus also implied that disease-associated haplotype blocks with polygenic effects were not only possible, but rather were highly plausible. Combined, these data demonstrate for the first time that multiple modifiers of hypertension can cosegregate at a single GWAS locus.

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The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor

Cited by 24 publications

References 36 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

Vascular protective effects of Astragalus membranaceus and its main constituents in rats with chronic hyperhomocysteinemia

Identifying multiple causative genes at a single GWAS locus

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