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Respiratory Research
Published in: Respiratory Research 1/2019

Open Access 01-12-2019 | Pulmonary Hypertension | Research

Identification of genetic factors underlying persistent pulmonary hypertension of newborns in a cohort of Chinese neonates

Authors: Xu Liu, Mei Mei, Xiang Chen, Yulan Lu, Xinran Dong, Liyuan Hu, Xiaojing Hu, Guoqiang Cheng, Yun Cao, Lin Yang, Wenhao Zhou

Published in: Respiratory Research | Issue 1/2019

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Abstract

Background

Persistent pulmonary hypertension of the newborn (PPHN) is a severe clinical problem among neonatal intensive care unit (NICU) patients. The genetic pathogenesis of PPHN is unclear. Only a few genetic polymorphisms have been identified in infants with PPHN. Our study aimed to investigate the potential genetic etiology of PPHN.

Methods

This study recruited PPHN patients admitted to the NICU of the Children’s Hospital of Fudan University from Jan 2016 to Dec 2017. Exome sequencing was performed for all patients. Variants in reported PPHN/pulmonary arterial hypertension (PAH)-related genes were assessed. Single nucleotide polymorphism (SNP) association and gene-level analyses were carried out in 74 PPHN cases and 115 non-PPHN controls with matched baseline characteristics.

Results

Among the patient cohort, 74 (64.3%) patients were late preterm and term infants (≥ 34 weeks gestation) and 41 (35.7%) were preterm infants (< 34 weeks gestation). Preterm infants with PPHN exhibited low birth weight and a high frequency of bronchopulmonary dysplasia, respiratory distress syndrome (RDS) and mortality. Nine patients (only one preterm infant) were identified as harboring genetic variants, including three with pathogenic/likely pathogenic variants in TBX4 and BMPR2 and six with variants of unknown significance in BMPR2, SMAD9, TGFB1, KCNA5 and TRPC6. Three SNPs (rs192759073, rs1047883 and rs2229589) in CPS1 and one SNP (rs1044008) in NOTCH3 were significantly associated with PPHN (p < 0.05). CPS1 and SMAD9 were identified as risk genes for PPHN (p < 0.05).

Conclusions

In this study, we identified genetic variants in PPHN patients, and we reported CPS1, NOTCH3 and SMAD9 as risk genes for late preterm and term PPHN in a single-center Chinese cohort. Our findings provide additional genetic evidence of the pathogenesis of PPHN and new insight into potential strategies for disease treatment.
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Metadata
Title
Identification of genetic factors underlying persistent pulmonary hypertension of newborns in a cohort of Chinese neonates
Authors
Xu Liu
Mei Mei
Xiang Chen
Yulan Lu
Xinran Dong
Liyuan Hu
Xiaojing Hu
Guoqiang Cheng
Yun Cao
Lin Yang
Wenhao Zhou
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2019
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-019-1148-1

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