title: Pharmacogenetics of drug-induced birth defects: what is known so far?
abstract: A literature review was performed to collect information on the role of pharmacogenetics in six proposed teratogenic mechanisms associated with drug use during pregnancy: folate antagonism, oxidative stress, angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism, cyclooxygenase-1 and -2 inhibition, 5-hydroxytryptamine-reuptake inhibition and drug transporters in the placenta. Data on the direct relationship between pharmacogenetics and drug-induced birth defects were found for folate metabolism, oxidative stress caused by phenytoin exposure and drug transporters in the placenta. Although no specific data to support pharmacogenetic-related birth defects were found for the NSAIDs, paroxetine and fluoxetine, it might be expected that polymorphisms modify their teratogenic effects. The usually low prevalence of drug-induced malformations impedes the demonstration of the contribution of pharmacogenetics. Large-scale studies, preferably case-control studies, are needed.
authors.affiliation: Unit of Pharmacoepidemiology & Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen 9713AV, The Netherlands. b.wilffert@znb.nl
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
authors.forename: Judith
authors.initials: J
authors.lastname: Altena
authors.forename: Laurien
authors.initials: L
authors.lastname: Tijink
authors.forename: Marleen M H J
authors.initials: MM
authors.lastname: van Gelder
authors.forename: Lolkje T W
authors.initials: LT
authors.lastname: de Jong-van den Berg
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000235:genetics*; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000013:Congenital Abnormalities / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D056726:Genetic Association Studies; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D013723:Teratogens / Q000633:toxicity
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D005493:Folic Acid Antagonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013723:Teratogens; D005492:Folic Acid