Supported by grants from NIDCR (K99-DE022378-01).
Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: An individual participant data pooled-analysis
Article first published online: 13 MAY 2013
Copyright © 2013 Wiley Periodicals, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 97, Issue 8, pages 509–514, August 2013
How to Cite
Butali, A., Little, J., Chevrier, C., Cordier, S., Steegers-Theunissen, R., Jugessur, A., Oladugba, B. and Mossey, P. A. (2013), Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: An individual participant data pooled-analysis. Birth Defects Research Part A: Clinical and Molecular Teratology, 97: 509–514. doi: 10.1002/bdra.23133
- Issue published online: 14 AUG 2013
- Article first published online: 13 MAY 2013
- Manuscript Accepted: 3 MAR 2013
- Manuscript Revised: 11 FEB 2013
- Manuscript Received: 11 DEC 2012
- cleft lip and palate;
- folic acid, individual patient data;
This study examines gene–environment interaction between the MTHFR C667T polymorphism and folic acid in the etiology of orofacial clefts (OFC). We used a pooled-analytical approach on four studies that used similar methods.
We used logistic regression to analyze the pooled sample of 1149 isolated cases and 1161 controls. Fetal and maternal MTHFR C677T genotypes, and maternal periconceptional exposure to smoking, alcohol, vitamin containing folic acid and folic acid supplements were contrasted between the cleft types [non-syndromic clefts lip or without cleft palate (CL(P)) and non-syndromic cleft palate (CP)] and control groups.
There was a reduced risk of CL(P) with maternal folic acid use (p = 0.008; OR = 0.70, 95% CI: 0.65–0.94) and with supplements containing folic acid (p = 0.028, OR = 0.80, 95% CI: 0.65–0.94). Maternal smoking increased the risk of both CL(P) (p < 10 e−3; OR = 1.62, 95% CI: 1.35–1.95) and CP (p = 0.028; OR = 1.38, 95% CI: 1.04–1.83). No significant risk was observed with either maternal or fetal MTHFR C677T genotypes.
This individual participant data (IPD) meta-analysis affords greater statistical power and can help alleviate the problems associated with aggregate-level data-sharing. The result of this IPD meta-analysis is consistent with previous reports suggesting that folic acid and smoking influence OFC outcomes. Birth Defects Research (Part A) 97:509-514, 2013. © 2013 Wiley Periodicals, Inc.