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Polymorphisms in CYP2C9 are associated with response to indomethacin among neonates with patent ductus arteriosus

Caitlin J Smith1, Kelli K Ryckman1, Timothy M Bahr2

  • 1Department of Epidemiology, University of Iowa, Iowa City, Iowa.

Pediatric Research
|June 14, 2017
PubMed

Insights

Genetic variations in CYP2C9 influence how preterm infants respond to indomethacin treatment for patent ductus arteriosus (PDA). Specific single-nucleotide polymorphisms (SNPs) are linked to successful PDA closure, suggesting personalized medicine approaches.

Area of Science:

  • Pharmacogenomics
  • Neonatal Medicine
  • Genetics

Background:

  • Patent ductus arteriosus (PDA) is a frequent complication in preterm infants.
  • Indomethacin is a standard treatment for PDA, with response variability.
  • Evidence indicates that indomethacin response is significantly heritable.

Purpose of the Study:

  • To investigate the association between single-nucleotide polymorphisms (SNPs) in the CYP2C9 gene and PDA closure in response to indomethacin.
  • To identify genetic markers that predict indomethacin efficacy in neonates.

Main Methods:

  • Analysis of six SNPs in CYP2C9 for association with indomethacin response.
  • Case-control study comparing responders and non-responders (requiring surgery).
  • Independent transmission disequilibrium tests in parent-child trios.

Main Results:

  • The G allele of rs2153628 was associated with increased odds of indomethacin response (OR: 1.918).
  • rs2153628 (G allele) and rs1799853 (T allele) were overtransmitted in responders, supporting the case-control findings.
  • These SNPs are linked to altered indomethacin metabolism.

Conclusions:

  • Two CYP2C9 SNPs, rs2153628 and rs1799853, are associated with indomethacin response in treating PDA.
  • Genetic polymorphisms in CYP2C9 may influence the effectiveness of indomethacin for PDA closure.
  • These findings support the potential for genotype-guided indomethacin therapy.

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