Interaction of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and folic acid levels in recurrent depression

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism associated with body fat accumulation could possibly trigger an inflammatory process by elevating homocysteine levels and increasing cytokine production, causing several diseases. This study aimed to evaluate the effects of food intervention, and not folate supplements, on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in overweight and obese women with the MTHFR C677T polymorphism. A randomized, double-blind eight-week clinical trial of 48 overweight and obese women was conducted. Participants were randomly assigned into two groups. They received 300 g of vegetables daily for eight weeks containing different doses of folate: 95 µg/day for Group 1 and 191 µg/day for Group 2. MTHFR C677T polymorphism genotyping was assessed by digestion with HinfI enzyme and on 12% polyacrylamide gels. Anthropometric measurements, 24-h dietary recall, and biochemical analysis (blood folic acid, vitamin B12, homocysteine (Hcy), TNF-α, IL-1β, and IL-6) were determined at the beginning and end of the study. Group 2 had a significant increase in folate intake (p < 0.001) and plasma folic acid (p < 0.05) for individuals with the cytosine–cytosine (CC), cytosine–thymine (CT), and thymine–thymine (TT) genotypes. However, only individuals with the TT genotype presented reduced levels of Hcy, TNF-α, IL-6, and IL-1β (p < 0.001). Group 1 showed significant differences in folate consumption (p < 0.001) and folic acid levels (p < 0.05) for individuals with the CT and TT genotypes. Food intervention with folate from vegetables increased folic acid levels and reduced interleukins, TNF-α, and Hcy levels, mainly for individuals with the TT genotype.

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The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment

Nutrients ◽

10.3390/nu12041147 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1147

Author(s):

Hee-Jin Kim ◽

Il Woong Sohn ◽

Young Seo Kim ◽

Jae-Bum Jun

Keyword(s):

Uric Acid ◽

Cognitive Impairment ◽

Folic Acid ◽

Vitamin B12 ◽

Dietary Intervention ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Vascular Lesion ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism

In an elderly population with cognitive impairment, we investigated the association between serum uric acid (sUA) and serum homocysteine (sHcy), known risk factors for cerebrovascular disease. We also investigated the potential effect of the C677T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) to the sUA level in different dementia types. Participants underwent a battery of tests including measurements of sUA, sHcy, folic acid, and vitamin B12 as well as genotyping of the MTHFR locus. Data from 861 subjects (597 females to 264 males) were retrospectively analyzed. Subjects with hyperhomocysteinemia had lower serum folic acid and vitamin B12 and higher sUA than those with normal sHcy. sUA was significantly associated with serum creatinine, HbA1c, and sHcy regardless of gender. The TT genotype was found to be associated with hyperhomocysteinemia in both genders (p = 0.001). The levels of hyperlipidemia, sHcy, and sUA differed according to dementia subtypes. High sUA were associated with hyperhomocystenemia in TT genotype only in dementia with vascular lesion. This study reveals that sUA is positively associated with sHcy. We speculate that the two markers synergistically increase cerebrovascular burden and suggested that dietary intervention for sUA and sHcy would be helpful for cognitive decline with vascular lesion.

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Association between Maternal and Fetal MTHFR C677T and MTRR A66G Polymorphisms with the Risk of NTDs: A Systematic Review and Meta-Analysis Study

10.32592/ircmj.2021.23.11.1350 ◽

2021 ◽

Keyword(s):

Folic Acid ◽

Subgroup Analysis ◽

Methylenetetrahydrofolate Reductase ◽

Meta Analysis ◽

Mthfr C677t ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism ◽

Analysis Study ◽

Methionine Synthase Reductase ◽

Mtrr A66g

Background: Neural tube defects (NTDs) are classed as multifactorial birth defects of the brain and spinal cord that arise during embryonic development. Although the etiology is not well understood, NTDs are reported to be prevented by maternal folic acid supplementation before and during early pregnancy. This meta-analysis study aimed to assess the association between fetal and maternal methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with the risk of NTDs. Methods: The PubMed, Scopus, and Springer Link databases were searched (from March 2000 to November 2020) for the literature on the association between MTHFR C677T and MTRR A66G polymorphisms with the risk of NTDs. Results: In total, 33 studies were reviewed in the present study, and it was revealed that, unlike MTRR A66G polymorphism, MTHFR C677T was statistically associated with the risk of NTDs in the overall population. The results of subgroup analysis showed that the Indian subcontinent subgroup with maternal MTHFR C677T polymorphism and the European subgroup with fetal MTHFR C677T polymorphism was significantly susceptible to NTDs. Conclusion: The obtained results revealed that, unlike MTRR A66G, maternal and fetal MTHFR C677T polymorphism was significantly associated with NTDs. Subgroup analysis also demonstrated that folic acid deprivation can be considered the main cause of MTHFR C677T polymorphism in some areas.

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Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC) infected patients from the Northeast of Brazil

Nutrition Journal ◽

10.1186/1475-2891-10-86 ◽

2011 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Erika RF Siqueira ◽

Cláudia PMS Oliveira ◽

Maria TC Muniz ◽

Filipe Silva ◽

Leila MMB Pereira ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

High Plasma ◽

Plasma Homocysteine ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism

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Effect of maternal serum B vitamins, homocysteine levels and the 5, 10‐methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on postnatal growth measurements in their infants

The FASEB Journal ◽

10.1096/fasebj.20.4.a602 ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Hyesook Kim ◽

Young Ju Kim ◽

Ki Nam Kim ◽

Namsoo Chang

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Postnatal Growth ◽

Maternal Serum ◽

B Vitamins ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism

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Effect of riboflavin supplementation on blood pressure and possible effect modification by the MTHFR C677T polymorphism: a randomised trial in rural Gambia

F1000Research ◽

10.12688/f1000research.25113.1 ◽

2020 ◽

Vol 9 ◽

pp. 1034

Author(s):

Modou Jobe ◽

Mary Ward ◽

Bakary Sonko ◽

Abdul Khalie Muhammad ◽

Ebrima Danso ◽

...

Keyword(s):

Blood Pressure ◽

Large Scale ◽

Methylenetetrahydrofolate Reductase ◽

Controlled Trial ◽

Randomised Trial ◽

Mthfr C677t ◽

C677t Polymorphism ◽

Phenotypic Effect ◽

Riboflavin Deficiency ◽

Mthfr C677t Polymorphism

Introduction: Emerging evidence links a functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene (rs1801133) with hypertension in adults. This variant reduces the affinity of MTHFR for its cofactor flavin-adenine dinucleotide (FAD) which is derived from riboflavin. Previous work has demonstrated a blood pressure (BP)-lowering effect of riboflavin in Irish adults with the MTHFR 677TT variant. We hypothesize that the almost-universal severe riboflavin deficiency seen in rural Gambia mimics the BP phenotypic effect of the TT variant and exacerbate the effect of the CT variant. We will test this in a randomised, placebo-controlled trial, whether intervention with riboflavin can decrease BP in adults in rural Gambia. Methods: This is a phase 2 recall-by-genotype randomised single-blind placebo-controlled riboflavin supplementation trial. We will use the Keneba biobank to recruit approximately 102 individuals aged between 18-70, previously genotyped for the MTHFR C677T polymorphism and identified as carrying the T allele; these individuals will be age- and sex-matched to a similar number of homozygotes for the C allele. The participants will be randomised to a 16-week supplementation trial of 5 mg/day riboflavin or placebo, supplied every 14 days. The primary outcome, BP, will be measured at baseline and at weeks 8 and 16. Blood samples, collected at baseline and week 16, will be analysed for riboflavin, homocysteine, red cell folate, cobalamin (vitamin B12) and pyridoxine (vitamin B6). Discussion: The study will evaluate the role of riboflavin supplementation in BP control within a population with high levels of riboflavin deficiency and will test a possible gene-nutrient interaction with the MTHFR C677T polymorphism. If improvements in BP are observed in this study, and proven in subsequent large-scale interventions, riboflavin could offer a cost-effective, safe and accessible option for the prevention and control of hypertension in this population. Trial registration: ClinicalTrials.gov Identifier NCT03151096. Registered on 12 May 2017.

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MTHFR Gene Polymorphism and Age of Onset of Schizophrenia and Bipolar Disorder

BioMed Research International ◽

10.1155/2014/318483 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Mohamed A. El-Hadidy ◽

Hanaa M. Abdeen ◽

Sherin M. Abd El-Aziz ◽

Mohammad Al-Harrass

Keyword(s):

Bipolar Disorder ◽

Healthy Subjects ◽

Methylenetetrahydrofolate Reductase ◽

Age Of Onset ◽

Age At Onset ◽

Mthfr C677t ◽

Control Group ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism ◽

Mthfr Gene Polymorphism

Objective. Several studies with contradictory results from different cultures about association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in schizophrenia and bipolar disorders. Little is known about this association in Arab culture and Egypt. So the present study aimed to assess the association of MTHFR C677T polymorphism in bipolar disorder (BD) and schizophrenia in comparison to control group. The association between MTHFR C677T polymorphism and the age at onset in schizophrenia or BD was also studied.Methods. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the genotype and allele frequencies of MTHFR C677T polymorphism in 149 healthy subjects and 134 bipolar and 103 schizophrenia patients.Results. In BD and schizophrenia, there was a higher prevalence of MTHFR C677T polymorphism than healthy subjects. Earlier age at onset was found in patients with BD, carrying one copy of the T allele or CT genotypes but not in patients with schizophrenia.Conclusion. The present findings suggest that the MTHFR C677T polymorphisms are likely to be associated with the risk of developing BD and schizophrenia and influence the age at onset of BD but not the age at onset of schizophrenia.

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