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