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Maternal medication use, carriership of the ABCB1 3435C > T polymorphism and the risk of a child with cleft lip with or without cleft palate
Author(s) -
Bliek Bart J.B.,
van Schaik Ron H.N.,
van der Heiden Ilse P.,
SayedTabatabaei Fakhredin A.,
van Duijn Cock M.,
Steegers Eric A.P.,
SteegersTheunissen Régine P.M.
Publication year - 2009
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33036
Subject(s) - offspring , genotype , pregnancy , medicine , gestation , obstetrics , risk factor , folic acid , polymorphism (computer science) , pediatrics , physiology , genetics , gene , biology
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.