Journal article
Patterns of Gene Expression in the Ductus Arteriosus Are Related to Environmental and Genetic Risk Factors for Persistent Ductus Patency
Pediatric research, Vol.68(4), pp.292-297
2010
DOI: 10.1203/PDR.0b013e3181ed8609
PMCID: PMC2940964
PMID: 20581741
Abstract
Three independent risk factors (immature gestation, absence of antenatal glucocorticoid exposure, and presence of the rs2817399(A) allele of the gene TFAP2B) are associated with patent ductus arteriosus (PDAs) that fail to close during prostaglandin inhibition. We hypothesized that these three factors may affect a common set of genes that increase the risk of persistent PDA after birth. We studied baboon ductus from term, preterm, and glucocorticoid-treated preterm fetuses and found that both immature gestation and absence of antenatal glucocorticoid exposure decreased RNA expression of calcium- and potassium-channel genes involved in oxygen-induced constriction, and phosphodiesterase genes (that modulate cAMP/cGMP signaling). Ductus obtained from second trimester human pregnancies were genotyped for TFAP2B polymorphisms. When present, the rs2817399(A) allele also was associated with decreased expression of calcium- and potassium-channel genes. In contrast, alleles of two other TFAP2B polymorphisms, rs2817419(G) and rs2635727(T), which are not related to the incidence of PDA after birth, had no effect on RNA expression. In conclusion, three calcium- and potassium-channel genes (CACNA1G/ alpha1G, CACNB 2/CaL-beta2, and KCNA2/ Kv1.2) were similarly affected by each of the PDA risk factors. We speculate that these channels may play a significant role in closing the preterm ductus during prostaglandin inhibition and may be potential targets for future pharmacologic manipulations.
Details
- Title: Subtitle
- Patterns of Gene Expression in the Ductus Arteriosus Are Related to Environmental and Genetic Risk Factors for Persistent Ductus Patency
- Creators
- Nahid WALEH - Pharmaceutical Discovery Division SRI International, Menlo Park, California 94025, United StatesRyan HODNICK - Department of Pediatrics University of New Mexico, Albuquerque, New Mexico 87131, United StatesNami JHAVERI - Department of Pediatrics Cardiovascular Research Institute, University of California San Francisco, California 94143, United StatesSuzanne MCCONAGHY - Department of Pediatrics University of New Mexico, Albuquerque, New Mexico 87131, United StatesJohn DAGLE - Department of Pediatrics University of Iowa, Iowa City, Iowa 52242, United StatesSteven SEIDNER - Department of Pediatrics University of Texas, Health Science Center, San Antonio, Texas 78229, United StatesDonald MCCURNIN - Department of Pediatrics University of Texas, Health Science Center, San Antonio, Texas 78229, United StatesJeffrey C MURRAY - Department of Pediatrics University of Iowa, Iowa City, Iowa 52242, United StatesRobin OHLS - Department of Pediatrics University of New Mexico, Albuquerque, New Mexico 87131, United StatesRonald I CLYMAN - Department of Pediatrics Cardiovascular Research Institute, University of California San Francisco, California 94143, United States
- Resource Type
- Journal article
- Publication Details
- Pediatric research, Vol.68(4), pp.292-297
- DOI
- 10.1203/PDR.0b013e3181ed8609
- PMID
- 20581741
- PMCID
- PMC2940964
- NLM abbreviation
- Pediatr Res
- ISSN
- 0031-3998
- eISSN
- 1530-0447
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- Language
- English
- Date published
- 2010
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Biochemistry and Molecular Biology; Dental Research; Neonatology
- Record Identifier
- 9984025286802771
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