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Patterns of gene expression in the ductus arteriosus are related to environmental and genetic risk factors for persistent ductus patency
- Source :
- Pediatric research. 68(4)
- Publication Year :
- 2010
-
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.
- Subjects :
- medicine.medical_specialty
Calcium Channels, L-Type
Single-nucleotide polymorphism
Gestational Age
Biology
Polymorphism, Single Nucleotide
Risk Assessment
Drug Administration Schedule
Article
Calcium Channels, T-Type
Pregnancy
Risk Factors
Internal medicine
Ductus arteriosus
Gene expression
medicine
Kv1.2 Potassium Channel
Animals
Humans
Genetic Predisposition to Disease
RNA, Messenger
Allele
Ductus Arteriosus, Patent
Glucocorticoids
Regulation of gene expression
Fetus
Gene Expression Regulation, Developmental
Ductus Arteriosus
Endocrinology
medicine.anatomical_structure
Logistic Models
Pediatrics, Perinatology and Child Health
Linear Models
Gestation
Female
Glucocorticoid
medicine.drug
Papio
Subjects
Details
- ISSN :
- 15300447
- Volume :
- 68
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Pediatric research
- Accession number :
- edsair.doi.dedup.....9a4a6939dfdbbbdab70d6e1e882f222c