title: Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: a multicenter case-control study.
abstract: Neural tube defects (NTDs) are severe congenital malformations due to failure of neural tube formation in early pregnancy. The proof that folic acid prevents NTDs raises the question of whether other parts of homocysteine (Hcy) metabolism may affect rates of NTDs. This French case-control study covered: 77 women aged 17-42 years sampled prior to elective abortion for a severe NTDs (cases) and 61 women aged 20-43 years with a normal pregnancy. Plasma and erythrocyte folate, plasma B6, B12 and Hcy were tested as five polymorphisms MTHFR 677 C --> T, MTHFR 1298 A --> C, MTR 2756 A --> G, MTTR 66 A --> G and TCN2 776 C --> G. Cases had significantly lower erythrocyte folate, plasma folate, B12 and B6 concentrations than the controls, and higher Hcy concentration. The odds ratio was 2.15 (95% CI: 1.00-4.59) for women with the MTRR 66 A --> G allele and it was decreased for mothers carrying the MTHFR 1298 A --> C allele. In multivariate analysis, only the erythrocyte folate concentration (P = 0.005) and plasma B6 concentration (P = 0.020) were predictors. Red cell folate is the main determinant of NTDs in France. Folic acid supplement or flour fortification would prevent most cases. Increased consumption of vitamins B12 and B6 could contribute to the prevention of NTDs. Genetic polymorphisms played only a small role. Until folic acid fortification becomes mandatory, all women of reproductive age should consume folic acid in a multivitamin that also contains B12 and B6.
authors.affiliation: Inserm U-145, Department of Biochemistry, CHU Nice Hôpital Pasteur, Nice, France. pantaleo.candito@wanadoo.fr
authors.forename: Mirande
authors.initials: M
authors.lastname: Candito
authors.forename: Romain
authors.initials: R
authors.lastname: Rivet
authors.forename: Bernard
authors.initials: B
authors.lastname: Herbeth
authors.forename: Catherine
authors.initials: C
authors.lastname: Boisson
authors.forename: René-Charles
authors.initials: RC
authors.lastname: Rudigoz
authors.forename: Dominique
authors.initials: D
authors.lastname: Luton
authors.forename: Hubert
authors.initials: H
authors.lastname: Journel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Oury
authors.forename: François
authors.initials: F
authors.lastname: Roux
authors.forename: Robert
authors.initials: R
authors.lastname: Saura
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vernhet
authors.forename: Pascal
authors.initials: P
authors.lastname: Gaucherand
authors.forename: Françoise
authors.initials: F
authors.lastname: Muller
authors.forename: Béatrice
authors.initials: B
authors.lastname: Guidicelli
authors.forename: Hélène
authors.initials: H
authors.lastname: Heckenroth
authors.forename: Patrice
authors.initials: P
authors.lastname: Poulain
authors.forename: Martine
authors.initials: M
authors.lastname: Blayau
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.forename: Laurence
authors.initials: L
authors.lastname: Roszyk
authors.forename: Cécile
authors.initials: C
authors.lastname: Brustié
authors.forename: Pascal
authors.initials: P
authors.lastname: Staccini
authors.forename: Philippe
authors.initials: P
authors.lastname: Gérard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fillion-Emery
authors.forename: Rosa-Maria
authors.initials: RM
authors.lastname: Guéant-Rodriguez
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Van Obberghen
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D005602:France; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009436:Neural Tube Defects / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D009752:Nutritional Status; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011446:Prospective Studies; D012307:Risk Factors; D014803:Vitamin B Complex / Q000097:blood / Q000378:metabolism*
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase