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

Caitlin J Smith; Kelli K Ryckman; Timothy M Bahr; John M Dagle

doi:10.1038/pr.2017.145

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

Journal article

Open access

Peer reviewed

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

Caitlin J Smith, Kelli K Ryckman, Timothy M Bahr and John M Dagle

Pediatric research, Vol.82(5), pp.776-780

11/2017

DOI: 10.1038/pr.2017.145

PMCID: PMC5645220

PMID: 28609430

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Abstract

BackgroundPatent ductus arteriosus (PDA) is a common complication seen in preterm infants. Indomethacin is routinely used to treat PDA. Evidence suggests that the response of indomethacin is highly heritable. This study investigated the association between single-nucleotide polymorphisms (SNPs) in CYP2C9 and the closure of PDA in response to indomethacin.MethodsSix SNPs in CYP2C9 were analyzed for association with indomethacin response. A case-control analysis was performed among neonates who responded to indomethacin (responders) and among those who required surgical ligation (non-responders). Independent transmission disequilibrium tests were performed among parent-child trios of responders and non-responders.ResultsThe G allele of rs2153628 was associated with increased odds of response to indomethacin in the case-control analysis (odds ratios (OR): 1.918, 95% confidence interval (CI): 1.056, 3.483). Among indomethacin responders, the G allele of rs2153628 and the T allele of rs1799853 were overtransmitted from the parents to their child (OR: 2.667, 95% CI: 1.374, 5.177 and OR: 2.375, 95% CI: 1.040, 5.425, respectively), consistent with the case-control analysis.ConclusionWe identified an association between two SNPs in CYP2C9, rs2153628 and rs1799853, and indomethacin response for the treatment of PDA. These findings suggest that response to indomethacin in the closure of PDA may be influenced by polymorphisms associated with altered indomethacin metabolism.

Ductus Arteriosus, Patent - genetics

Pharmacogenetics

Ductus Arteriosus, Patent - drug therapy

Gene Frequency

Humans

Risk Factors

Male

Case-Control Studies

Cytochrome P-450 CYP2C9 - genetics

Drug Resistance - genetics

Indomethacin - pharmacokinetics

Ductus Arteriosus, Patent - enzymology

Indomethacin - therapeutic use

Ligation

Ductus Arteriosus, Patent - diagnosis

Anti-Inflammatory Agents, Non-Steroidal - therapeutic use

Treatment Failure

Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics

Pharmacogenomic Variants

Female

Polymorphism, Single Nucleotide

Odds Ratio

Cytochrome P-450 CYP2C9 - metabolism

Infant, Newborn

Details

Title: Subtitle: Polymorphisms in CYP2C9 are associated with response to indomethacin among neonates with patent ductus arteriosus
Creators: Caitlin J Smith - Department of Epidemiology, University of Iowa, Iowa City, Iowa
Kelli K Ryckman - Department of Epidemiology, University of Iowa, Iowa City, Iowa
Timothy M Bahr - Division of Neonatology, Department of Pediatrics, University of Iowa, Iowa City, Iowa
John M Dagle - Division of Neonatology, Department of Pediatrics, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Pediatric research, Vol.82(5), pp.776-780
Publisher: United States
DOI: 10.1038/pr.2017.145
PMID: 28609430
PMCID: PMC5645220
ISSN: 0031-3998
eISSN: 1530-0447
Grant note: R01 HD057192 / NICHD NIH HHS R01 HD052953 / NICHD NIH HHS R01 HL109199 / NHLBI NIH HHS R00 HD065786 / NICHD NIH HHS K99 HD065786 / NICHD NIH HHS
Language: English
Date published: 11/2017
Academic Unit: Stead Family Department of Pediatrics; Epidemiology; Biochemistry and Molecular Biology; Neonatology
Record Identifier: 9983995044802771

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