Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease

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

Journal of Nutrition ◽

10.1093/jn/88.4.375 ◽

1966 ◽

Vol 88 (4) ◽

pp. 375-381 ◽

Cited By ~ 20

Author(s):

James C. Woodard ◽

Paul M. Newberne

Keyword(s):

Vitamin B12 ◽

Carbon Metabolism ◽

One Carbon Metabolism

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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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