title: Angiotensin II type 1 receptor A1166C polymorphism and prophylactic indomethacin treatment induced ductus arteriosus closure in very low birth weight neonates.
abstract: Altered pulmonary vascular resistance might be a factor for delayed closure of the ductus arteriosus (DA) in preterm infants. Angiotensin II plays a central role in the elevation of pulmonary vascular resistance. Angiotensin II exerts its vasoconstrictor effect on the angiotensin II type 1 receptor (AT1R). Homozygous carriers of the AT1R A1166C genetic variant present an exaggerated vasoconstrictor response to angiotensin II. We have investigated whether the presence of AT1R CC1166 influences the effect of prophylactic indomethacin treatment on the closure of DA until the fifth postnatal day in preterm infants. In this retrospective study detailed medical history of the first postnatal week was obtained in 159 infants born before the 33rd gestational week. All were treated by prophylactic indomethacin to induce permanent closure of the DA. On the sixth postnatal day the DA was still open in 56, whereas it was permanently closed in 103. The AT1R A1166C genotype of the infants was determined from Guthrie spots. Stepwise binary logistic regression analysis was used to assess the effect of medical conditions and genotype on the risk of patent DA (PDA). Birth weight, infantile respiratory distress, and severe hypotension were independent risk factors for PDA (p < 0.01, p < 0.05, p < 0.05, respectively). The carrier state of AT1R CC1166 was protective against PDA (p < 0.05; odds ratio, 0.067). AT1R AC1166 genotype was not associated with PDA. Our results indicate that the risk of PDA might be lower in infants of AT1R CC1166 than in those with AC or AA genotypes.
authors.affiliation: First Department of Pediatrics, University Semmelweiss Budapest, Budapest, H-1083 Hungary.
authors.forename: Andras
authors.initials: A
authors.lastname: Treszl
authors.forename: Miklos
authors.initials: M
authors.lastname: Szabo
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Dunai
authors.forename: Andras
authors.initials: A
authors.lastname: Nobilis
authors.forename: Istvan
authors.initials: I
authors.lastname: Kocsis
authors.forename: Tamas
authors.initials: T
authors.lastname: Machay
authors.forename: Tivadar
authors.initials: T
authors.lastname: Tulassay
authors.forename: Barna
authors.initials: B
authors.lastname: Vasarhelyi
mesh_terms: D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use*; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D011110:Polymorphism, Genetic; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D002317:Cardiovascular Agents; D044140:Receptor, Angiotensin, Type 1; D007213:Indomethacin