Genetic Modifiers of Patent Ductus Arteriosus in Term Infants

J Pediatr. 2016 Sep;176:57-61.e1. doi: 10.1016/j.jpeds.2016.05.066. Epub 2016 Jun 22.


Objective: To identify single-nucleotide polymorphisms (SNPs) in specific candidate genes associated with patent ductus arteriosus in term infants.

Study design: We conducted an initial family-based, candidate gene study to analyze genotype data from DNA samples obtained from 171 term infants and their parents enrolled in the National Birth Defects Prevention Study (NBDPS). We performed transmission disequilibrium testing (TDT) using a panel of 55 SNPs in 17 genes. Replication of SNPs with P < .1 in the NBDPS trios was performed with a case-control strategy in an independent population.

Results: TDT analysis of the NBDPS trios resulted in 6 SNPs reaching the predetermined cutoff (P < .1) to be included in the replication study. These 6 SNPs were genotyped in the independent case-control population. A SNP in TGFBR2 was found to be associated with term patent ductus arteriosus in both populations after we corrected for multiple comparisons. (rs934328, TDT P = 2 × 10(-4), case-control P = 6.6 × 10(-5)).

Conclusions: These findings confirm the importance of the transforming growth factor-beta pathway in the closure of the term ductus arteriosus and may suggest new therapeutic targets.

Keywords: CREBB; TGFBR2; TRAF1; candidate gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Ductus Arteriosus, Patent / genetics*
  • Genes, Modifier*
  • Genetic Association Studies
  • Genotype
  • Humans
  • Infant, Newborn
  • Polymorphism, Single Nucleotide*
  • Term Birth