title: Genetics of patent ductus arteriosus susceptibility and treatment.
abstract: The ductus arteriosus is a vital fetal structure designed to close shortly after birth. Although many physiologic and pharmacologic investigations have characterized the closure of this structure, genetic studies of persistent patency of the ductus arteriosus (patent ductus arteriosus, PDA) are relatively recent. Progress in the identification of specific genes associated with PDA is well behind that of many adult-onset diseases because of several reasons ranging from the lack of large biorepositories for this unique population to the belief that any genetic contribution to PDA is minimal. Viewing the PDA as a complex, developmentally influenced disease with both genetic and environmental risk factors has resulted in initial successes in some genetic studies. We will introduce several genetic approaches, which have been or are currently being applied to the study of PDA, that have been successful in identifying polymorphisms associated with adult diseases. Genetic investigations of PDA will be discussed with respect to heritability, in general, and to specific risk genes. Several animal models that have been used to study PDA-related genes will also be presented. Further advances in discovering genetic variation causing PDA will drive the more rational use of current therapies, and may help identify currently unknown targets for future therapeutic manipulation.
authors.affiliation: Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Hanine
authors.initials: H
authors.lastname: Hajj
authors.forename: John M
authors.initials: JM
authors.lastname: Dagle
mesh_terms: D000818:Animals; D003285:Contractile Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004285:Dogs; D004374:Ductus Arteriosus, Patent / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D064448:Filamins; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D051663:Kv1.2 Potassium Channel / Q000235:genetics; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D018398:Homeodomain Proteins; D051663:Kv1.2 Potassium Channel; C509903:MYH11 protein, human; D008840:Microfilament Proteins; D018125:Receptors, Transforming Growth Factor beta; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C493677:TFAP2B protein, human; D050656:Transcription Factor AP-2; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D018995:Myosin Heavy Chains