Relation of Vitamin B12 and One-carbon Metabolism to Hydrocephalus in the Rat

The folate, vitamin B12 and vitamin B6 (one-carbon) metabolic pathway is essential for the synthesis of precursors used in DNA synthesis, repair, and methylation. We hypothesise that single nucleotide polymorphisms in genes encoding enzymes in this pathway can disrupt these processes leading to adverse pregnancy outcomes. We investigated associations of six candidate polymorphisms in five genes related to one-carbon metabolism with risk for adverse pregnancy outcome in 586 nulliparous Caucasian couples with normal fertility. Chi-square analysis was used to compare genotype frequencies with pregnancy outcomes. Pregnancies were classified as healthy (n=261), preeclampsia (PE, n=38), gestational hypertension (GHT, n=32), small-for-gestational-age (SGA, n=60) and PE+SGA (n=22). Associations between maternal, paternal and neonatal genotypes with customised birthweight centiles and placental weight were determined using ANOVA with SIDAK post-hoc analyses. The maternal MTR 2756 G allele was associated with decreased placental weight (–87g, P=0.040). Both paternal and neonatal MTR 2756 G alleles were associated with lower birthweight (–12%, P=0.028 and –10%, P=0.039) while the latter was also associated with PE+SGA (P <0.000). Neonatal MTRR GG genotype was associated with GHT and PE with SGA (P=0.033, P=0.011). Neonatal MTHFD1 GG genotype was twice as frequent in PE and GHT (P=0.037; P=0.019) while neonatal TCN2 GG genotype doubled in SGA (P=0.042) compared with healthy pregnancies. Our findings indicate that genetic variation in multiple one-carbon metabolism genes may influence risk of adverse pregnancy outcome. MTR with cofactor vitamin-B12, catalyses the methylation of homocysteine to methionine. Formation of methionine through this pathway is important for synthesis of phospholipids, proteins, myelin, DNA, RNA and S-adenosyl methionine. TCN2 encodes the vitamin-B12 transport protein and MTHFD1 catalyses the conversion of one-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymine and purine synthesis and are important for healthy placental and fetal development. Larger studies are needed to further examine gene/gene and gene/diet interactions in this pathway.

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Balanced Essential Micronutrients during Pregnancy: High Concern

Journal of Nutritional Biology ◽

10.18314/jnb.v4i2.1373 ◽

2018 ◽

Vol 4 (2) ◽

pp. 259-261

Author(s):

Srilatha Bashetti ◽

Kumar SaiSailesh ◽

Aparna Varma ◽

Rajagopalan Vijayaraghavan

Keyword(s):

Folic Acid ◽

Vitamin B12 ◽

Neural Tube ◽

Neural Tube Defects ◽

Carbon Metabolism ◽

Strong Predictor ◽

Fetal Loss ◽

Folate Deficiency ◽

Cobalamin Deficiency ◽

One Carbon Metabolism

Nutrition and epigenetic changes is the emerging topic of interest in the present scenario to understand the effects of increased supplementation of micronutrients like Folic Acid (FA). The study is taken up in the public health interest, to evaluate the importance of balancing the different micronutrients in the diet to avoid unbalanced nutritional disorders and other health complications later in life. It has been hypothesized that disease risks after birth or later in life can be determined by paternal or maternal diet. This raised an interest to study in-utero effects of environmental exposures like air pollution, toxins, nutrition, etc. It had been assumed that during embryonic period most of the dividing tissues get exposed to the environmental insults and that change results in predisposition of cancer or other health outcomes. There could be the possibility of maternal exposures like nutrition may alter the intrauterine one-carbon metabolism or the precursor milieu and may be involved in the disruption of one-carbon metabolism in developing offspring. Modification in methyl me of offspring with subsequent changes in phenotypes has been noted in the preliminary studies with increased folic acid (FA) supplementation during pregnancy. Maternal folate deficiency has been implicated as a cause of prematurity and both folate deficiency and cobalamin deficiency have been implicated in recurrent fetal loss and neural tube defects. Folic acid supplementation at the time of conception and in the first 12 weeks of pregnancy is expected to reduce by 70% the incidence of neural tube defects (NTDs) (meningomyelocele, encephalocele and spina bifida) in the fetus. Most of the protective effect can be achieved by taking folic acid, 0.4 mg daily at the time of conception. However there is no clear relationship between maternal folatestatus and the fetal abnormalities. It has been observed that, the lower the maternal folate, the greater the risk to the fetus. On the other hand maternal cobalamin status is a strong predictor of vitamin B12 in breastfed infants up to at least 6 months of age. Because of the transfer from mother to offspring during pregnancy and lactation, maternal requirements during this period are increased and deficiency may occur. The influence of low vitamin B12 during pregnancy may have cognitive ability of children later in life. Hypothyroidism is caused by insufficient production of thyroid hormones by the thyroid gland. In females, hypothyroidism is associated mainly with oligomenorrhea.

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Levels of Folate and Vitamin B12, and Genetic Polymorphisms Involved in One-Carbon Metabolism May Increase the Risk of Cervical Cytological Abnormalities

Nutrition and Cancer ◽

10.1080/01635581.2021.2022723 ◽

2021 ◽

pp. 1-10

Author(s):

Nayara Nascimento Toledo Silva ◽

Ana Carolina Silva Santos ◽

Maria de Fátima Dias de Sousa Brito ◽

Diama Bradha Andrade Peixoto do Vale ◽

Cláudia Martins Carneiro ◽

...

Keyword(s):

Vitamin B12 ◽

Genetic Polymorphisms ◽

Carbon Metabolism ◽

Cytological Abnormalities ◽

One Carbon Metabolism ◽

Folate And Vitamin B12

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Epigenetics and One Carbon Metabolism: The Role of Folate and Vitamin B12

Turkiye Klinikleri Journal of Internal Medicine ◽

10.5336/intermed.2018-62699 ◽

2018 ◽

Vol 3 (3) ◽

pp. 95-101

Author(s):

Aslı YİĞİT ◽

Fatma Esra GÜNEŞ

Keyword(s):

Vitamin B12 ◽

Carbon Metabolism ◽

One Carbon Metabolism ◽

Folate And Vitamin B12

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The Vitamins Involved in One-Carbon Metabolisms are Associated with Reduced Risk of Breast Cancer in Overall and Subtypes

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000501 ◽

2020 ◽

Vol 90 (1-2) ◽

pp. 131-140 ◽

Cited By ~ 3

Author(s):

Mahshid Hatami ◽

Farhad Vahid ◽

Mohammad Esmaeil Akbari ◽

Mahya Sadeghi ◽

Fatemeh Ameri ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin B12 ◽

Carbon Metabolism ◽

Vitamin B6 ◽

Regulation Of Gene Expression ◽

Folate Intake ◽

Her2 Status ◽

Total Intake ◽

One Carbon Metabolism ◽

The Relationship

Abstract. Background: Some micronutrients like folate, vitamin B12, B6, and B2 are the source of coenzymes, which participate in one-carbon metabolism. Any disruption in this metabolism can interfere with DNA replication, repair and regulation of gene expression and ultimately promote the likelihood of carcinogenesis. This study aimed at investigating the relationship between the intakes of micronutrients involved in one-carbon metabolism with breast cancer (BrCa) and its subtype’s odds. Methods: Nutrients’ intake from diet and supplements were collected through interviewing 151 cases and 154 controls by a 168-item semiquantitative food frequency questionnaire. Logistic regression was used to determine the relationship between dietary and/or total intake of studied nutrients and odds of BrCa and its subtypes. Results: After adjusting the effects of confounding variables in the models, the odds of BrCa was significantly lower in the highest intake quartile compared with the lowest quartile for total intake of vitamin B2 (OR = 0.17, 95% CI, 0.07–0.39; Ptrend < 0.001), vitamin B6 (OR = 0.11, 95% CI, 0.05–0.27; Ptrend < 0.001), vitamin B12 (OR = 0.20, 95% CI, 0.09–0.43; Ptrend < 0.001) and folate (OR = 0.09, 95% CI, 0.04–0.21; Ptrend < 0.001). Also, those with the highest quartile of vitamin B6, B12, B2 and folate intake compared with the lowest quartile were less likely to develop estrogen receptor (ER)+ and progesterone receptor (PR)+ subtypes, ER- status, PR- and human epidermal growth factor receptor 2 (HER2)+ subtypes and HER2- status. Conclusion: High intakes of vitamins B2, B6 and folate are associated with reduced odds of BrCa in overall and all ER, PR and HER2 subtypes. Also, high intakes of vitamin B12 reduced the odds of all subtypes of BrCa except ER- subtype.

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B vitamin blood concentrations and one-carbon metabolism polymorphisms in a sample of Italian women and men attending a unit of transfusion medicine: a cross-sectional study

European Journal of Nutrition ◽

10.1007/s00394-020-02448-1 ◽

2020 ◽

Author(s):

Renata Bortolus ◽

Francesca Filippini ◽

Silvia Udali ◽

Marianna Rinaldi ◽

Sabrina Genesini ◽

...

Keyword(s):

Vitamin B12 ◽

Carbon Metabolism ◽

Vitamin B6 ◽

Blood Donors ◽

Cross Sectional Study ◽

Transfusion Medicine ◽

Sectional Study ◽

Cross Sectional ◽

Plasma Folate ◽

One Carbon Metabolism

Abstract Purpose To define blood status of folate, vitamin B12, vitamin B6, homocysteine, and major one-carbon metabolism-related polymorphisms in healthy, males and females blood donors, aged 18–65 years were evaluated. General characteristics and lifestyle factors were also investigated. Methods An explorative cross-sectional study design was used to evaluate a sample of blood donors attending the Unit of Transfusion Medicine of the Verona University Hospital, Italy. From April 2016 to May 2018, 499 subjects were enrolled (255 men, 244 women of whom 155 of childbearing age). Major clinical characteristics including lifestyle and dietary habits, B vitamins and homocysteine were analyzed. The MTHFR 677 C>T, cSHMT 1420 C>T, DHFR 19 bp ins/del, RFC1 80 G>A polymorphisms were also determined. Results Mean plasma concentrations of folate, vitamin B12, vitamin B6 and homocysteine were 14.2 nmol/L (95% CI 13.7–14.8), 271.9 pmol/L (95% CI 262.6–281.5), 51.0 nmol/L (95% CI 48.7–53.4) and 13.5 µmol/L (95% CI 13.1–14.0), respectively. Plasma folate, was adequate (> 15 nmol/L) in 44.7% of all subjects, 39.0% of males and 42.5% of women < 45 years. Similarly, vitamin B12 was adequate (> 350 pmol/L) in 25.1% of all subjects and in 20.3% of men ≥ 45 years. The rare allele frequencies were 0.21 for MTHFR 677TT, 0.11 for cSHMT 1420TT, 0.18 for DHFR 19 bp del/del, 0.20 for RFC1 80AA, and a gene–nutrient interaction was confirmed for folate concentrations according to MTHFR 677C>T and DHFR 19 bp del/del. Conclusion An Italian sample of healthy blood donors shows that an adequate concentration of plasma folate and vitamin B12 is reached only in a limited percentage of subjects, thus encouraging consideration for specific public health strategies.

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