Folate and vitamin B12-related genes and risk for omphalocele

James L Mills; Tonia C Carter; Denise M Kay; Marilyn L Browne; Lawrence C Brody; Aiyi Liu; Paul A Romitti; Michele Caggana; Charlotte M Druschel

doi:10.1007/s00439-011-1117-3

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Folate and vitamin B12-related genes and risk for omphalocele

Journal article

Peer reviewed

Folate and vitamin B12-related genes and risk for omphalocele

James L Mills, Tonia C Carter, Denise M Kay, Marilyn L Browne, Lawrence C Brody, Aiyi Liu, Paul A Romitti, Michele Caggana and Charlotte M Druschel

Human genetics, Vol.131(5), pp.739-746

05/2012

DOI: 10.1007/s00439-011-1117-3

PMCID: PMC3374579

PMID: 22116453

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https://www.ncbi.nlm.nih.gov/pmc/articles/3374579View

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Abstract

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.

Genetic Predisposition to Disease

Humans

Vitamin B 12 - genetics

Genotype

Risk

Homocysteine - genetics

Pilot Projects

Methylenetetrahydrofolate Reductase (NADPH2) - genetics

Polymorphism, Single Nucleotide

Folic Acid - genetics

Hernia, Umbilical - genetics

Infant, Newborn

Receptors, Cell Surface - genetics

Details

Title: Subtitle: Folate and vitamin B12-related genes and risk for omphalocele
Creators: James L Mills - Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS, Bethesda, MD 20892, USA. jamesmills@nih.gov
Tonia C Carter
Denise M Kay
Marilyn L Browne
Lawrence C Brody
Aiyi Liu
Paul A Romitti
Michele Caggana
Charlotte M Druschel
Resource Type: Journal article
Publication Details: Human genetics, Vol.131(5), pp.739-746
DOI: 10.1007/s00439-011-1117-3
PMID: 22116453
PMCID: PMC3374579
NLM abbreviation: Hum Genet
ISSN: 1432-1203
eISSN: 1432-1203
Publisher: Germany
Grant note: HHSN267200703431C / PHS HHS N01-DK-7-3431 / NIDDK NIH HHS ZIA HD008792-05 / Intramural NIH HHS ZIA HD008792-03 / Intramural NIH HHS ZIA HD008792-04 / Intramural NIH HHS
Language: English
Date published: 05/2012
Academic Unit: Epidemiology; Biostatistics
Record Identifier: 9983995132602771

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