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.
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Abbreviations
- AngII:
-
angiotensin II
- AT1R:
-
AngII type 1 receptors
- AT1R A1166C:
-
polymorphism substituting C for A at position +1166 of AT1R gene
- DA:
-
ductus arterious
- PDA:
-
patent ductus arteriosus
- ACE:
-
angiotensin-converting enzyme
- PKU:
-
phenylketonuria
- IRDS:
-
infantile respiratory distress syndrome
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Acknowledgements
The authors thank Dr. László Zubovics from Schöpf-Mérei Women's Hospital for his help in the enrollment of patients and Dr. Ágnes Schuler from PKU laboratory for her help in obtaining blood samples.
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Supported financially by OTKA Grants T031950-F032024, K+F 0134/2001, and ETT-281/2001. Barna Vásárhelyi is a recipient of the Bolyai János Research Grant of the Hungarian Academy of Sciences.
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Treszl, A., Szabó, M., Dunai, G. et al. Angiotensin II Type 1 Receptor A1166C Polymorphism and Prophylactic Indomethacin Treatment Induced Ductus Arteriosus Closure in Very Low Birth Weight Neonates. Pediatr Res 54, 753–755 (2003). https://doi.org/10.1203/01.PDR.0000088016.67117.39
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DOI: https://doi.org/10.1203/01.PDR.0000088016.67117.39
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