scholarly journals Riboflavin as a Determinant of Plasma Total Homocysteine: Effect Modification by the Methylenetetrahydrofolate Reductase C677T Polymorphism

2000 ◽  
Vol 46 (8) ◽  
pp. 1065-1071 ◽  
Author(s):  
Steinar Hustad ◽  
Per Magne Ueland ◽  
Stein Emil Vollset ◽  
Ying Zhang ◽  
Anne Lise Bjørke-Monsen ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Multiple Linear Regression Model ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Serum Folate ◽  
Flavin Mononucleotide ◽  
Cross Sectional ◽  
Plasma Thcy ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

Abstract Background: Plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. tHcy concentrations are partly determined by folate, cobalamin, and vitamin B6 status, and methylenetetrahydrofolate reductase (MTHFR) and other flavoenzymes are important for the biotransformation of these vitamins. This motivates the investigation of the possible relationship between riboflavin status and tHcy. Methods: The study had a cross-sectional design and included 423 healthy blood donors, ages 19–69 years. We determined plasma tHcy, serum folate, serum cobalamin, serum creatinine, and MTHFR C677T genotype. In addition, we measured riboflavin and its two coenzyme forms, flavin mononucleotide and flavin adenine dinucleotide, in EDTA plasma by capillary electrophoresis and laser-induced fluorescence detection. Results: Riboflavin determined tHcy independently in a multiple linear regression model with adjustment for sex, age, folate, cobalamin, creatinine, and MTHFR genotype (P = 0.008). tHcy was 1.4 μmol/L higher in the lowest compared with the highest riboflavin quartile. The riboflavin-tHcy relationship was modified by genotype (P = 0.004) and was essentially confined to subjects with the C677T transition of the MTHFR gene. Conclusions: Plasma riboflavin is an independent determinant of plasma tHcy. Studies on deficient populations are needed to evaluate the utility of riboflavin supplementation in hyperhomocysteinemia.

scholarly journals The effect of 677C → T and 1298A → C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects

2000 ◽  
Vol 83 (6) ◽  
pp. 593-596 ◽  
Author(s):  
A. Chango ◽  
A. Chango ◽  
F. Boisson ◽  
F. Barbé ◽  
D. Quilliot ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Specific Activity ◽  
Reductase Activity ◽  
Mthfr Gene ◽  
High Serum ◽  
Serum Folate ◽  
Vitamin B ◽  
Serum Folate Level ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

We have studied the effect of common mutations (677C → T and 1298A → C) of the methylenetetrahydrofolate reductase (MTHFR) gene in sixty-six healthy French subjects, aged 27–47 years. Serum folate, vitamin B12, and plasma total homocysteine were measured as well as the specific activity of MTHFR in lymphocytes. The frequency of subjects homozygous for the 677TT genotype was 18 %, and that of those homozygous for the 1298CC genotype was 12·5 %. The frequency of individuals heterozygous for both mutations was 23·5 %. The 1298A → C mutation was associated with decreased MTHFR specific activity in subjects with both 677CC and 677CT genotypes. This activity was 60 % for the 677CC/1298AC genotype and 52 % for the 677CC/1298CC genotype when compared with the MTHFR specific activity of the 677CC/1298AA genotype. Heterozygotes for both mutations (677CT/1298AC genotype) had 36 % of the reference specific activity. Although homocysteine levels in 677TT and 1298CC genotype subjects were higher than for other genotypes, no significant differences were observed among different genotypes. This may be due to high serum folate level in our samples, and suggests that folate therapy may be useful to prevent hyperhomocysteinaemia in homozygous mutant subjects.

Hyperhomocysteinemia and C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene in Patients with Cardiovascular Disease

Pteridines ◽  
2010 ◽  
Vol 21 (1) ◽  
pp. 103-109
Author(s):  
Zahira Houcher ◽  
Bakhouche Houcher ◽  
Abderezak Touabti ◽  
Samia Begag ◽  
Ayşenur Öztürk ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Old Patients ◽  
Mthfr C677t Polymorphism ◽  
Plasma Thcy ◽  
C677t Mutation ◽  
Total Homocysteine ◽  
And Gender

Abstract The aim of the present study was to explore the influence of age and gender, on the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma total homocysteine (tHcy) concentrations in patients with cardiovascular disease (CVD). Fasting tHcy and the MTHFR C677T mutation were evaluated in 98 patients with CVD, 46 were men and 52 women (aged 20-96 years). There was a significant elevation of plasma tHcy with age (<45 yr: 33.9 μmol/L vs. >75 yr: 43.6 μmol/L; p <0.01). The mean tHcy concentration increased significantly with age in men (<55 yr: 33.4 μmol/L vs. >55yr: 42.45 μmol/L; p 0.01). However, the plasma tHcy was not increased with older age in women. The frequency of the TT genotype was 19.6% in the younger patients group (>55 yr) compared with 4.7% in the older patients group (>55 yr; p <0.01). In conclusion, the data presented here are consistent with genetic factors that influence tHcy levels being more prominent in old patients (>55 yr). Then, the MTHFR mutation does not seem to be associated with either high tHcy or the occurrence of CVD.

scholarly journals Plasma Total Homocysteine, Folate, and Vitamin B12 Status and Hospitalizations for Cardiovascular Disease

Pteridines ◽  
2007 ◽  
Vol 18 (1) ◽  
pp. 122-127
Author(s):  
Bakhouche Houcher ◽  
Mirande Candito ◽  
Pierre Gibelin
Keyword(s):  
Vitamin B12 ◽  
Serum Vitamin ◽  
Inverse Correlation ◽  
Serum Folate ◽  
Plasma Thcy ◽  
Total Homocysteine ◽  
Group 2 ◽  
Folate And Vitamin B12 ◽  
Plasma Total Homocysteine ◽  
Group 1

Abstract Elevated plasma total homocysteine (tHcy) is an independent risk factor for cardiovascular disease (CVD). Also known is that plasma folate and vitamin B12 influence homocysteine metabolism as cosubstrate and cofactor, respectively. This population-based study was conducted to evaluate the plasma concentrations of tHcy, folate, and vitamin B12 in 54 older patients aged ≥51 years (40 males; 14 females) of Nice hospital cardiology service. After excluding cases with a serum creatinine >120 mmol/L, we established the test properties of a plasma tHcy concentration <15 μmol/L (Group 1) or ≥15 μmol/L (Group 2). In the population aged ≥51 years, plasma tHcy was higher in women (18.0 μmol/L) than in men (15.5 μmol/L; not significant), conversely, serum vitamin B12 was higher in men (376.9 pg/ml) than in women (340.7 pg/ml; not significant). Average plasma tHcy was 11.5 μmol/L in Group 1 and 21.6 μmol/L in Group 2. Vice versa, serum vitamin B12 was higher in Group 1 (419.5 pg/ml) than in Group 2 (307.2 pg/ml) (p <0.05). Correlation analysis (Pearson's r) in the total study population (20-84 years) indicated an inverse correlation between serum folate and age (r = -0.231, p <0.05). In the subjects, aged ≥51 years, there was a significant negative correlation between age and tHcy levels (r = -0.283, p <0.05) and serum vitamin B12 concentrations (r = -0.326, p <0.01) but not with serum folate. However, in subjects with tHcy <15 μmol/L, a significant inverse correlation existed between plasma tHcy and serum folate (r = -0.455; p <0.05). In conclusion, these results highlight the relevance of the vitamin status and particularly of folate levels in the modulation of fasting tHcy levels in the patients with clinical hyperhomocysteinemia, defined as plasma tHcy >15 μmol/L.

Homocysteine, folate, methylene tetrahydrofolate reductase genotype and vascular morbidity in diabetic subjects

2002 ◽  
Vol 102 (6) ◽  
pp. 631-637 ◽  
Author(s):  
Joey M. KAYE ◽  
Kim G. STANTON ◽  
Vincent J. MCCANN ◽  
Samuel D. VASIKARAN ◽  
Valerie BURKE ◽  
...  
Keyword(s):  
Vascular Disease ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Plasma Homocysteine ◽  
Serum Folate ◽  
Type I ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Mthfr Genotype ◽  
Erythrocyte Folate

In the present study, the determinants of fasting plasma homocysteine in diabetic subjects were examined; whether plasma homocysteine and vascular disease are related and the influence of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene on serum and erythrocyte folate, plasma homocysteine and vascular disease. Diabetic clinic subjects (Type I, n = 354; Type II, n = 392) were recalled for a cross-sectional survey. Standard methods were used to measure biochemical variables and to characterize vascular disease and MTHFR genotype. Plasma homocysteine was significantly and directly related to age, male sex and serum urea, and inversely related to serum folate and vitamin B12, independently in stepwise regression. When corrected for age and sex, homocysteine was significantly related to hard end points of coronary artery disease and stroke (each P<0.01), remaining significant when additionally adjusted for serum folate (P = 0.043 and P = 0.019 respectively). Serum folate was not clearly related to these events, although there was a trend to associate with the lower quintile of serum folate. The MTHFR genotype was not a determinant of plasma homocysteine, even in those in the lowest quintile of serum folate, nor of vascular disease. TT homozygosity at residue 677 was associated with elevation of total erythrocyte folate compared with both other genotypes (P<0.0001), almost certainly due to the diversion of 5,10-methylenetetrahydrofolate into derivates subsequent to the partial metabolic block that results from the MTHFR enzyme defect. In conclusion, in this clinic cohort of people with diabetes, vascular disease is related to plasma homocysteine, which is correlated with serum folate. The MTHFR genotype does not significantly influence either plasma homocysteine or vascular disease, despite it being a determinant of erythrocyte folate, which reflects its effect on folate metabolism.

scholarly journals Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis

2013 ◽  
Vol 109 (5) ◽  
pp. 785-794 ◽  
Author(s):  
Derek Obersby ◽  
David C. Chappell ◽  
Andrew Dunnett ◽  
Amalia A. Tsiami
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Elevated Plasma ◽  
Cross Sectional ◽  
Animal Products ◽  
Plasma Thcy ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B12can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B12deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B12levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B12of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B12did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B12, from which it can be concluded that the usual dietary source of vitamin B12is animal products and those who choose to omit or restrict these products are destined to become vitamin B12deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.

scholarly journals An evidence-based approach to globally assess the covariate-dependent effect of MTHFR SNP rs1801133 on plasma homocysteine: a systematic review and meta-analysis

2017 ◽  
Author(s):  
Huifeng Jin ◽  
Haojie Cheng ◽  
Wei Chen ◽  
Xiaoming Sheng ◽  
Mark Brown ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Evidence Based ◽  
Single Nucleotide ◽  
Dependent Effect ◽  
The Public ◽  
Modifying Effect ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

BackgroundThe single nucleotide polymorphism (SNP) of the gene Methylenetetrahydrofolate Reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for a rs1801133 carrier.ObjectiveWe hypothesized that variability of this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers and/or confounders, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates.DesignWe systematically extracted from published studies the data of tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting meta-dataset was first used to analyze the covariates’ modifying effect by meta regression and other statistical means. Subsequently, we stratified tHcy data by the rs1801133 genotypes and analyzed under each genotype the variability of the risk resulted from the covariates’ confounding.ResultsThe dataset contains data of 36 rs1801133 covariates that were collected from 114,448 subjects and 249 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification and, to a larger degree, confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner.Conclusionswe demonstrated an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public that increasingly receives genetic data from commercial services without interpretation of its clinical relevance.

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