Effects of polymorphisms in endothelial nitric oxide synthase and folate metabolizing genes on the concentration of serum nitrate, folate, and plasma total homocysteine after folic acid supplementation: A double-blind crossover study

Cabo, Rona; Hernes, Sigrunn; Slettan, Audun; Haugen, Margaretha; Ye, Shu; Blomhoff, Rune; Mansoor, M. A.

doi:10.1016/j.nut.2014.08.009

Cited by 5 publications

(5 citation statements)

References 47 publications

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“…The resulting product sizes for the gene polymorphisms are given in Table 1. Details of the PCR methods have been provided previously (Cabo et al 2015).…”

Section: Genotypingmentioning

confidence: 99%

Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study

et al. 2015

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Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study Abstract Data on the effect of combined genetic polymorphisms, involved in folate metabolism, on the concentration of serum folate after folic acid supplementation are scarce. Therefore, we investigated the impact of seven gene polymorphisms on the concentration of serum folate and p-tHcy in healthy subjects after short-term folic acid supplementation. In a randomized, double blind, crossover study, apparently healthy subjects were given either 0.8 mg folic acid per day (n = 46) or placebo (n = 45) for 14 days. The washout period was 14 days. Fasting blood samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid supplementation (n = 91) and on placebo (n = 45) were used for the statistical analysis. The concentration of serum folate increased higher in subjects with higher age (53.5 ± 7.0 years) than in subjects with lower age (24.3 ± 3.2 years) after folic acid supplementation (p = 0.006). The baseline concentration of serum folate in subjects with polymorphism combination, reduced folate carrier protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT?TT, was lower than RFC1-80 AA and MTHFR677 CT?TT (p = 0.002). After folic acid supplementation, a higher increase in the concentration of serum folate was detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC than RFC1-80 GG and MTHFR CT?TT combination (p \ 0.0001). The baseline concentration of plasma total homocysteine (p-tHcy) was altered by combined polymorphisms in genes associated with folate metabolism. After folic acid supplementation, in subjects with combined polymorphisms in methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the concentration of p-tHcy was changed (p = 0.002). The combination of RFC1-80 and MTHFR-677 polymorphisms had a profound affect on the concentration of serum folate in healthy subjects before and after folic acid supplementation.

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“…The resulting product sizes for the gene polymorphisms are given in Table 1. Details of the PCR methods have been provided previously (Cabo et al 2015).…”

Section: Genotypingmentioning

confidence: 99%

Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study

et al. 2015

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“…Acute exercise seems to be associated with active demethylation pathways. The mechanism proposed for active demethylation involves ten-eleven translocation (TET) proteins, suggesting that metabolites produced during exercise could alter the activity of TET proteins ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…The DNA methylation was analyzed at the baseline and after the 14 weeks of training. Salting-out technique ( 20 ) was used to extract DNA from leukocytes. Biodrop spectrophotometry was used to assess DNA quality and concentration using.…”

Section: Methodsmentioning

confidence: 99%

14-weeks combined exercise epigenetically modulated 118 genes of menopausal women with prediabetes

et al. 2022

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BackgroundPre-diabetes precedes Diabetes Mellitus (DM) disease and is a critical period for hyperglycemia treatment, especially for menopausal women, considering all metabolic alterations due to hormonal changes. Recently, the literature has demonstrated the role of physical exercise in epigenetic reprogramming to modulate the gene expression patterns of metabolic conditions, such as hyperglycemia, and prevent DM development. In the present study, we hypothesized that physical exercise training could modify the epigenetic patterns of women with poor glycemic control.Methods48 post-menopause women aged 60.3 ± 4.5 years were divided according to their fasting blood glucose levels into two groups: Prediabetes Group, PG (n=24), and Normal Glucose Group, NGG (n=24). All participants performed 14 weeks of physical exercise three times a week. The Infinium Methylation EPIC BeadChip measured the participants’ Different Methylated Regions (DMRs).ResultsBefore the intervention, the PG group had 12 DMRs compared to NGG. After the intervention, five DMRs remained different. Interestingly, when comparing the PG group before and after training, 118 DMRs were found. The enrichment analysis revealed that the genes were related to different biological functions such as energy metabolism, cell differentiation, and tumor suppression.ConclusionPhysical exercise is a relevant alternative in treating hyperglycemia and preventing DM in post-menopause women with poor glycemic control.

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“…As other markers are also related to the folate metabolic pathway (e.g. nitric oxide, Figure 1), the effects of polymorphisms in the endothelial nitric oxide synthase gene, as well as in additional folate metabolizing genes, on the concentration of serum nitrate need further attention [42]. Future assessments of these and other markers could shed some light on the significance of the observed association.…”

Section: Discussionmentioning

confidence: 99%

Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy

Jiménez-Ramírez

Castro

Ortiz

et al. 2017

Drug Metabolism and Personalized Therapy

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Background The study was conducted to investigate potential association between MTHFR genotypes and diabetic peripheral neuropathy (DPN) in Puerto Ricans with type-2 diabetes mellitus (T2DM) treated with metformin. The prevalence of major MTHFR polymorphisms in this cohort was also ascertained. Methods DNAs from 89 metformin-treated patients with T2DM and DPN were genotyped using the PCR-based RFLP assay for MTHFR677C > T and 1298A > C polymorphisms. Frequency distributions of these variants in the study cohort were compared to those reported for three reference populations (HapMap project) and controls (400 newborn specimens). Chi-square (or Fischer’s exact) tests and odds ratios (OR) were used to assess association with DPN susceptibility risk (patients vs. controls) and biochemical markers (wild types vs. carriers). Results Sixty-seven percent (67%) of participants carry at least one of these MTHFR polymorphisms. No deviations from Hardy-Weinberg equilibrium were detected. The genotype and allele frequencies showed statistically significant differences between participants and controls (p < 0.0001 and p = 0.03, respectively). Results suggest that 1298A > C but not 677C > T is associated with DPN susceptibility in this cohort (p = 0.018). Different patterns of allelic dissimilarities are observed when comparing our cohort vs. the three parental ancestries. After sorting individuals by their carrier status, no significant associations were observed between these genetic variants (independently or combined) and any of the biochemical markers (HbA1c, folate, vitamin B12, homocysteine). Conclusions Prevalence of major MTHFR variants in Puerto Rican patients with T2DM is first time ever reported. The study provides further evidence on the use of this genetic marker as an independent risk factor for DPN.

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Effects of polymorphisms in endothelial nitric oxide synthase and folate metabolizing genes on the concentration of serum nitrate, folate, and plasma total homocysteine after folic acid supplementation: A double-blind crossover study

Cited by 5 publications

References 47 publications

Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study

Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study

14-weeks combined exercise epigenetically modulated 118 genes of menopausal women with prediabetes

Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy

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