title: Maternal medication use, carriership of the ABCB1 3435C > T polymorphism and the risk of a child with cleft lip with or without cleft palate.
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.
authors.affiliation: Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bart J B
authors.initials: BJ
authors.lastname: Bliek
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Ilse P
authors.initials: IP
authors.lastname: van der Heiden
authors.forename: Fakhredin A
authors.initials: FA
authors.lastname: Sayed-Tabatabaei
authors.forename: Cock M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002971:Cleft Lip / Q000209:etiology*; D002972:Cleft Palate / Q000209:etiology*; D004198:Disease Susceptibility; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006579:Heterozygote; D006801:Humans; D009035:Mothers; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1