title: Folate-related genes and omphalocele.
abstract: Women who take folic acid in the periconceptional period greatly reduce their chances of having a child with a neural tube defect (NTD). Using multivitamins may also reduce the risk of having a child with an omphalocele. In this study, we tested single nucleotide polymorphisms in folate-related enzyme genes for association with omphalocele. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (MTHFD1), the reduced folate carrier (SLC19A1), and transcobalamin II (TCN2) were examined in 25 children with euploid omphalocele and 59 matched controls. Omphalocele cases were significantly more likely to carry the T allele of MTHFR 677C-->T, a known risk factor for NTDs (odds ratio 3.50, 95% confidence interval 1.07-11.47, P=0.035). The MTHFD1 R653Q, SLC19A1 R27H, and TCN2 P259R polymorphisms showed no significant association with omphalocele. In this small study, the thermolabile variant of MTHFR, 677C-->T, was associated with an increased risk for omphalocele. This variant causes reduced enzyme activity, thus suggesting a mechanism by which multivitamins with folic acid might prevent omphalocele. Additional investigation is required.
authors.affiliation: Division of Epidemiology, Statistics and Prevention Research, NICHD, NIH, DHHS, Bethesda, Maryland 20892, USA. jamesmills@nih.gov
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Druschel
authors.forename: Faith
authors.initials: F
authors.lastname: Pangilinan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pass
authors.forename: Christopher
authors.initials: C
authors.lastname: Cox
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Seltzer
authors.forename: Mary R
authors.initials: MR
authors.lastname: Conley
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000378:metabolism*; D005787:Gene Frequency; D005838:Genotype; D006554:Hernia, Umbilical / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008423:Maternal Age; D026901:Membrane Transport Proteins / Q000235:genetics; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009518:New York; D020641:Polymorphism, Single Nucleotide; D016742:Preconception Care; D011247:Pregnancy; D058978:Reduced Folate Carrier Protein; D014155:Transcobalamins / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D014155:Transcobalamins; D004247:DNA; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)