description) The investigators propose to apply state-of-the-art pharmacogenetic and pharmacoepidemiologic research methods and two large pharmacoepidemiologic databases to assess the genetically-mediated role of prescription and OTC medications in the etiology of human birth defects. A particular focus relates to the increased risk of a common birth defect, persistent pulmonary hypertension (PPHN) of the newborn, following exposure late in pregnancy to nonsteroidal anti-inflammatory drugs (NSAIDs), and particularly ibuprofen, a drug that is among the most commonly used agents in pregnancy.
In aim 1, the investigators will apply data from an ongoing epidemiologic study of PPHN to test the hypothesis that this increased risk is related to genetically mediated factors involved in the metabolism of NSATDs.
In aim 2, they propose to use sophisticated technologic approaches to identify mutations in the CYP2D6, CYP3A4, and CYP3A7 and other gene promoters that modify developmental and tissue-specific expression of those genes in the fetus and newborn. Once polymorphisms are identified, the investigators will systematically evaluate their possible etiologic roles in humans by applying these new tools to current and future data collected by the SEU-BDS and the CDC-NBDPS, two large and unique epidemiologic birth defect studies that collect both genetic material and detailed information on antenatal drug exposures.
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