title: Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: An individual participant data pooled-analysis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA. Azeez-butali@uiowa.edu
authors.forename: Azeez
authors.initials: A
authors.lastname: Butali
authors.forename: Julian
authors.initials: J
authors.lastname: Little
authors.forename: Cécile
authors.initials: C
authors.lastname: Chevrier
authors.forename: Sylvian
authors.initials: S
authors.lastname: Cordier
authors.forename: Regine
authors.initials: R
authors.lastname: Steegers-Theunissen
authors.forename: Astanand
authors.initials: A
authors.lastname: Jugessur
authors.forename: Bola
authors.initials: B
authors.lastname: Oladugba
authors.forename: Peter A
authors.initials: PA
authors.lastname: Mossey
mesh_terms: D000328:Adult; D001921:Brain / Q000002:abnormalities*; D016022:Case-Control Studies; D002971:Cleft Lip / Q000209:etiology* / Q000235:genetics*; D002972:Cleft Palate / Q000209:etiology* / Q000235:genetics*; D019587:Dietary Supplements; D000431:Ethanol / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000378:metabolism
chemical_list: D000431:Ethanol; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: MTHFR; cleft lip and palate; folic acid, individual patient data; pooled-analysis