vitamin-b-12 and Hernia--Umbilical

Both taking folic acid-containing vitamins around conception and consuming food fortified with folic acid have been reported to reduce omphalocele rates. Genetic factors are etiologically important in omphalocele as well; our pilot study showed a relationship with the folate metabolic enzyme gene methylenetetrahydrofolate reductase (MTHFR). We studied 169 non-aneuploid omphalocele cases and 761 unaffected, matched controls from all New York State births occurring between 1998 and 2005 to look for associations with single nucleotide polymorphisms (SNPs) known to be important in folate, vitamin B12, or choline metabolism. In the total study population, variants in the transcobalamin receptor gene (TCblR), rs2232775 (p.Q8R), and the MTHFR gene, rs1801131 (c.1298A>C), were significantly associated with omphalocele. In African-Americans, significant associations were found with SNPs in genes for the vitamin B12 transporter (TCN2) and the vitamin B12 receptor (TCblR). A SNP in the homocysteine-related gene, betaine-homocysteine S-methyltransferase (BHMT), rs3733890 (p.R239Q), was significantly associated with omphalocele in both African-Americans and Asians. Only the TCblR association in the total population remained statistically significant if Bonferroni correction was applied. The finding that transcobalamin receptor (TCblR) and transporter (TCN2) SNPs and a BHMT SNP were associated with omphalocele suggests that disruption of methylation reactions, in which folate, vitamin B12, and homocysteine play critical parts, may be a risk factor for omphalocele. Our data, if confirmed, suggest that supplements containing both folic acid and vitamin B12 may be beneficial in preventing omphaloceles.

Topics: Folic Acid; Genetic Predisposition to Disease; Genotype; Hernia, Umbilical; Homocysteine; Humans; Infant, Newborn; Methylenetetrahydrofolate Reductase (NADPH2); Pilot Projects; Polymorphism, Single Nucleotide; Receptors, Cell Surface; Risk; Vitamin B 12

Levels of folate, vitamin B12, the vitamin B12 binding proteins, apotranscobalamin I, II and III (TC I, II and III) and the unsaturated vitamin B12 binding capacity (UBBC) were measured in mid-trimester amniotic fluids from normal pregnancies, and from those where the fetus had open spina bifida, anencephaly or omphalocoele, and where the fetus was normal but the mother had had a previous neural tube defect pregnancy. At 15-19 weeks' gestation, vitamin B12 levels were low in the fluids of all the types of abnormal fetuses, and also of normal fetuses where there had been a previous NTD sib. In contradistinction, TC I, II and III and UBBC levels were generally abnormally high in all these groups. Low vitamin B12 levels in the face of high carrier protein levels suggest deranged vitamin B12 production or transport. Since these abnormalities are present in fluids from normal sibs of NTD individuals as well as from those with midline lesions, an inherited defect is implied. We propose that at least part of the genetic predisposition to NTD, and possibly other midline defects, could reside in an abnormality connected with vitamin B12 production, transport or metabolism, and a mechanism is suggested.

Topics: Amniotic Fluid; Anencephaly; Carrier Proteins; Female; Folic Acid; Hernia, Umbilical; Humans; Neural Tube Defects; Pregnancy; Pregnancy Trimester, Second; Spina Bifida Occulta; Transcobalamins; Vitamin B 12

Topics: Animals; Choline; Congenital Abnormalities; Deficiency Diseases; Diet; Embryonic and Fetal Development; Estrus; Female; Fertility; Fetal Death; Folic Acid; Formaldehyde; Glycine; Growth; Hernia, Umbilical; Hydrocephalus; Kidney Cortex Necrosis; Male; Niacinamide; Nutritional Requirements; Oxidation-Reduction; Pregnancy; Rats; Reproduction; Sarcosine; Spinal Dysraphism; Vitamin B 12