Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: a multicenter case-control study.
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.
Candito
Mirande
M
Inserm U-145, Department of Biochemistry, CHU Nice Hôpital Pasteur, Nice, France. pantaleo.candito@wanadoo.fr
Rivet
Romain
R
Herbeth
Bernard
B
Boisson
Catherine
C
Rudigoz
René-Charles
RC
Luton
Dominique
D
Journel
Hubert
H
Oury
Jean-François
JF
Roux
François
F
Saura
Robert
R
Vernhet
Isabelle
I
Gaucherand
Pascal
P
Muller
Françoise
F
Guidicelli
Béatrice
B
Heckenroth
Hélène
H
Poulain
Patrice
P
Blayau
Martine
M
Francannet
Christine
C
Roszyk
Laurence
L
Brustié
Cécile
C
Staccini
Pascal
P
Gérard
Philippe
P
Fillion-Emery
Nathalie
N
Guéant-Rodriguez
Rosa-Maria
RM
Van Obberghen
Emmanuel
E
Guéant
Jean-Louis
JL
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*
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