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

• Published in: American journal of medical genetics. Part A Vol. 149A; no. 10; pp. 2088 - 2092
• Main Authors: Bliek, Bart J.B., van Schaik, Ron H.N., van der Heiden, Ilse P., Sayed-Tabatabaei, Fakhredin A., van Duijn, Cock M., Steegers, Eric A.P., Steegers-Theunissen, Régine P.M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-10-2009
• Subjects: Adolescent; Adult; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Case-Control Studies; Child; Cleft Lip - etiology; Cleft Palate - etiology; Disease Susceptibility; Drug-Related Side Effects and Adverse Reactions; drugs; Female; gene-environment; Heterozygote; Humans; MDR-1; Mothers; orofacial clefts; P-glycoprotein; Polymorphism, Single Nucleotide - physiology; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - genetics; Risk Factors; Young Adult
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.33036

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.