Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2013 Aug;97(8):509-14.
doi: 10.1002/bdra.23133. Epub 2013 May 13.

Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: An individual participant data pooled-analysis

Azeez Butali  1 , Julian Little, Cécile Chevrier, Sylvian Cordier, Regine Steegers-Theunissen, Astanand Jugessur, Bola Oladugba, Peter A Mossey
Affiliations
Meta-Analysis

Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: An individual participant data pooled-analysis

Azeez Butali et al. Birth Defects Res A Clin Mol Teratol. 2013 Aug.

Abstract

Background: 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.

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.

Results: 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.

Conclusion: 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.

Keywords: MTHFR; cleft lip and palate; folic acid, individual patient data; pooled-analysis.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

None

References

    1. Beaty TH, Ruczinski I, Murray JC, et al. Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate. Genet Epidemiol. 2011;35:469–478. - PMC - PubMed
    1. Boyles AL, Wilcox AJ, Taylor JA, et al. Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts. Am J Med Genet A. 2008;146A:440–449. - PMC - PubMed
    1. Chevrier C, Perret C, Bahuau M, et al. Fetal and maternalMTHFRC677T genotype, maternal folate intake and the risk of nonsyndromic oral clefts. Am J Med Genet A. 2007;143:248–257. - PubMed
    1. De-Regil LM, Fernández-Gaxiola AC, Dowswell T, et al. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2010 CD007950. Issue 10. - PMC - PubMed
    1. Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate:understanding genetic and environmental influences. Nat Rev Genet. 2011;12:167–178. - PMC - PubMed

Publication types

Supplementary concepts

LinkOut - more resources