Maternal medication use, carriership of the ABCB1 3435C > T polymorphism and the risk of a child with cleft lip with or without cleft palate

Authors

  • Bart J.B. Bliek,

    1. Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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  • Ron H.N. van Schaik,

    1. Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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  • Ilse P. van der Heiden,

    1. Department of Epidemiology/Genetic Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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  • Fakhredin A. Sayed-Tabatabaei,

    1. Medicines Evaluation Board Agency, The Hague, The Netherlands
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  • Cock M. van Duijn,

    1. Department of Epidemiology/Genetic Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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  • Eric A.P. Steegers,

    1. Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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  • Régine P.M. Steegers-Theunissen,

    Corresponding author
    1. Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
    2. Department of Epidemiology/Genetic Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
    3. Department of Pediatric Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
    4. Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
    5. Department of Epidemiology, Radboud University Medical Center, Nijmegen, The Netherlands
    • Associate Professor in Reproductive Epidemiology, Departments of Obstetrics and Gynecology, Epidemiology, Pediatric Cardiology, and Clinical Genetics, Erasmus MC, University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
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  • the Eurocran Gene–Environment Interaction Group


  • How to cite this article: Bliek BJB, van Schaik RHN, van der Heiden IP, Sayed-Tabatabaei FA, van Duijn CM, Steegers EAP, Steegers-Theunissen RPM, the Eurocran Gene–Environment Interaction Group. 2009. Maternal medication use, carriership of the ABCB1 3435C > T polymorphism and the risk of a child with cleft lip with or without cleft palate. Am J Med Genet Part A 149A:2088–2092.

Abstract

Gene–environment interactions in the periconceptional period play an increasing role in the pathogenesis of birth defects, including cleft lip and/or cleft palate (CL/P). The P-glycoprotein, encoded by the ABCB1 gene, is suggested to protect the developing embryo from medication and other xenobiotic exposures. Furthermore, maternal medication use during early pregnancy is a significant risk factor for CL/P offspring. Therefore, the aim of this study is to investigate the association between the maternal and child's functional ABCB1 3435C > T polymorphism, periconceptional medication exposure, and the risk of a child with CL/P. A case–control study was performed among 175 mothers and 98 of their children with CL/P and 83 control mothers and their 65 children. Information on medication and folic acid use was collected. Mothers carrying the 3435TT genotype and using medication showed a 6.2-fold (95% CI = 1.6–24.2) increased risk of having a child with CL/P compared to mothers carrying the 3435CC genotype and not using medication. Periconceptional folic acid use reduced this risk by approximately 30% (OR = 3.9, 95% CI = 0.9–18.0). Mothers carrying the 3435TT genotype, using medication and not taking folic acid showed the highest risk estimate (OR = 19.2, 95% CI = 1.0–369.2). These data suggest that mothers who carry the ABCB1 3435C > T polymorphism are at significantly increased risk for having offspring with CL/P, especially mothers using medication in the periconceptional period. © 2009 Wiley-Liss, Inc.

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