Genetic Modifiers of Patent Ductus Arteriosus in Term Infants

Overview

Journal J Pediatr

Specialty Pediatrics

Date 2016 Jun 27

PMID 27344223

Citations 5

Authors

Priti M Patel

Allison M Momany

Kendra L Schaa

Paul A Romitti

Charlotte Druschel

Margaret E Cooper

Mary L Marazita

Jeffrey C Murray

John M Dagle

Affiliations

Soon will be listed here.

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.

Citing Articles

Ductus Arteriosus in Fetal and Perinatal Life.

Pugnaloni F, Doni D, Lucente M, Fiocchi S, Capolupo I J Cardiovasc Dev Dis. 2024; 11(4).

PMID: 38667731 PMC: 11050351. DOI: 10.3390/jcdd11040113.

Risk stratification of hemodynamically significant patent ductus arteriosus by clinical and genetic factors.

Chen Y, Xiao T, Chen H, Chen X, Wang Y, Ni Q World J Pediatr. 2023; 19(12):1192-1202.

PMID: 37318723 DOI: 10.1007/s12519-023-00733-7.

Next Generation Sequencing Identify Rare Copy Number Variants in Non-syndromic Patent Ductus Arteriosus.

Chen B, Hou A, Zhao L, Liu Y, Shi X, Du B Front Genet. 2020; 11:600787.

PMID: 33281884 PMC: 7689032. DOI: 10.3389/fgene.2020.600787.

Genetic variants associated with patent ductus arteriosus in extremely preterm infants.

Dagle J, Ryckman K, Spracklen C, Momany A, Cotten C, Levy J J Perinatol. 2018; 39(3):401-408.

PMID: 30518802 PMC: 6391165. DOI: 10.1038/s41372-018-0285-6.

Novel drug targets for ductus arteriosus manipulation: Looking beyond prostaglandins.

Shelton E, Singh G, Nichols C Semin Perinatol. 2018; 42(4):221-227.

PMID: 29880312 PMC: 6064654. DOI: 10.1053/j.semperi.2018.05.004.

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