Journal Article

Does the Interaction between Maternal Folate Intake and the Methylenetetrahydrofolate Reductase Polymorphisms Affect the Risk of Cleft Lip with or without Cleft Palate?

Iris A. L. M. van Rooij, Christl Vermeij-Keers, Leo A. J. Kluijtmans, Marga C. Ocké, Gerhard A. Zielhuis, Sieneke M. Goorhuis-Brouwer, Jan-Jaap van der Biezen, Anne-Marie Kuijpers-Jagtman and Régine P. M. Steegers-Theunissen

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 157, issue 7, pages 583-591
Published in print April 2003 | ISSN: 0002-9262
Published online April 2003 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwg005
Does the Interaction between Maternal Folate Intake and the Methylenetetrahydrofolate Reductase Polymorphisms Affect the Risk  of Cleft Lip with or without Cleft Palate?

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Periconceptional folic acid supplementation may reduce the risk of cleft lip with or without cleft palate (CL(P)). Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methyltetrahydrofolate, the predominant circulating form of folate. To determine the effect of MTHFR C677T and MTHFR A1298C genotypes and haplotypes on CL(P) risk and the interaction with maternal periconceptional dietary folate and folic acid supplement intake, the authors conducted a case-control triad study in the Netherlands (1998–2000) among 179 CL(P) and 204 control families. Infant and parental MTHFR C677T and MTHFR A1298C genotypes and haplotypes were not associated with CL(P) risk in the case-control and transmission disequilibrium test analyses. Mothers carrying the MTHFR 677TT genotype and who either did not use folic acid supplements periconceptionally or had a low dietary folate intake, or both, had an increased risk of delivering a CL(P) child (odds ratio (OR) = 5.9, 95% confidence interval (CI): 1.1, 30.9; OR = 2.8, 95% CI: 0.7, 10.5; OR = 10.0, 95% CI: 1.3, 79.1, respectively). No supplement use, low dietary folate intake, and maternal MTHFR 1298CC genotype increased the risk of CL(P) offspring almost sevenfold (OR = 6.5, 95% CI: 1.4, 30.2). Thus, the detrimental effect of low periconceptional folate intake on the risk of giving birth to a CL(P) child was more pronounced in mothers with the MTHFR 677TT or MTHFR 1298CC genotype.

Keywords: abnormalities; folic acid; genes; nutrition; pregnancy; vitamins; Abbreviations: CI, confidence interval; CL(P), cleft lip with or without cleft palate; MTHFR, methylenetetrahydrofolate reductase; OR, odds ratio.

Journal Article.  5979 words. 

Subjects: Public Health and Epidemiology

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