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

Genetic Modifiers of Patent Ductus Arteriosus in Term Infants.

Author information

1
Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL, US.
2
Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA US.
3
Department of Veterans Affairs, Office of Research and Development, Washington, D.C., US.
4
Department of Epidemiology, University of Iowa, Iowa City, IA, US.
5
Congenital Malformations Registry, New York State Department of Health, Albany, NY, US.
6
Dept of Epidemiology and Biostatistics, University of Albany School of Public Health, Rensselaer, NY, US.
7
Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, PA, US.
8
Department of Human Genetics, University of Pittsburgh, PA, US.
#
Contributed equally

Abstract

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

PMID:
27344223
PMCID:
PMC5003735
DOI:
10.1016/j.jpeds.2016.05.066
[Indexed for MEDLINE]
Free PMC Article

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