Skip to main content
  • Meeting abstract
  • Open access
  • Published:

Genetic factors predisposing to bronchopulmonary dysplasia. A pilot study by exome sequencing and pathways analysis


Bronchopulmonary Dysplasia (BPD) is a multifactorial disease with a significant genetic component. Twin studies indicate that heritability of BPD is estimated at 53 to 79% [1]. Association studies have identifiedseveral potential candidate genes encoding components of innate immune and antioxidant defenses, mechanisms of vascular and lung remodeling, matrix remodeling proteins, surfactantproteins [2, 3]. We planned a prospective multicentre study aimedto identify rare genetic variants contributing to the BPD phenotypeby exome sequencing using next-generation sequencing (NGS) technology.

Materials and methods

26 unrelated newborns with a clinicaldiagnosis of severe BPDaccording with NIH Consensus Criteria[4]were selected among a collected cohort of 366premature neonates of European origin with gestational age ≤ 32 wfrom 12Italiancenters. Genomic DNAwas extracted from peripheral blood and exome sequencing was carried out on an IlluminaHiSeq2000 platform. In order to identify potentially interesting variants related to BPD pathogenesis, we adopted two different strategies: 1) Candidate genes previously associated with BPD in association studies 2) Prioritization analysis based on pathways potentially involved in the pathogenesis of BPD (ToppGene Prioritization tool).


1) Candidate genes: we identified a total of 61variants in 19 candidate genes previously associated with BPD and confirmed them with Sanger; 31 are commonpolymorphism, 25 are rare and classified as dbSNPrs with a MAF <0.05and 6 are novel. Considering all the variants, the most mutated genes are those belonging to the TLR-family (TLR10, TLR1, TLR4), to oxidative stress-related genes (EPHX2, MTHFR, EPHX1)and to surfactant metabolism genes (SFTPD, ABCA3).2) Prioritizationanalysis: we decided to focus first on the list of the top 5 genes: TLR1, MMP1, NOS2, CRP and LBP. To evaluate the possible interaction between candidate genes previously associated with BPD and showing variants in our sample(ABCA3, SFTPD, SPOCK2, ACE, MTHFR, EPHX1, EPHX2, TLR5, TLR10, TLR1, TLR6, TLR4, GSTP1, MBL2, TLR10, TLR2) and the top 5 genes (NOS2, TLR1, MMP1, CRP, LBP) highlighted with prioritization analysis we usedString 9.122. The results allow the possibility of a networking with a main focus ongenes involved in inflammation (figure 1)[5].

Figure 1
figure 1

network including genes previously associated with BPD susceptibility and the 5 genes highlighted by toppGene analysis


In consideration of the results obtained in this pilot study, we canconclude that our approachmay be interesting to initiate the dissectionof genetic pathogenesis of BPD.Our study indicates that genes regarding inflammatory response and tissue remodeling may be relevant in BPD pathogenesis. These preliminary resultsneed to be confirmed and may contribute in improving knowledge of pathogenesis of BPD and targeting therapeutic interventions.


  1. Lavoie PM, Pham C, Jang KL: Heritability of bronchopulmonary dysplasia, defined according to the consensus statement of the national institutes of health. Pediatrics. 2008, 122: 479-485. 10.1542/peds.2007-2313.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Bhandari V, Gruen JR: The genetics of bronchopulmonary dysplasia. SeminPerinatol. 2006, 30: 185-191.

    Google Scholar 

  3. Shaw GM, O'Brodovich HM: Progress in understanding the genetics ofbronchopulmonary dysplasia. SeminPerinatol. 2013, 37: 85-93.

    Google Scholar 

  4. Jobe AH, Bancalari E: Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001, 163: 1723-1729. 10.1164/ajrccm.163.7.2011060.

    Article  CAS  PubMed  Google Scholar 

  5. Carrera P, Di Resta C, Volonteri C, Castiglioni E, Bonfiglio S, Lazarevic D, Cittaro D, Stupka E, Ferrari M, Somaschini M: Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study. Clin Chim Acta. 2015, S0009-8981(15)00007-8.

    Google Scholar 

Download references


We would like to thank the association “Un RespiroNelFuturoOnlus”

Author information

Authors and Affiliations



Corresponding author

Correspondence to Marco Somaschini.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Somaschini, M., Resta, C.D., Volonteri, C. et al. Genetic factors predisposing to bronchopulmonary dysplasia. A pilot study by exome sequencing and pathways analysis. Ital J Pediatr 41 (Suppl 1), A42 (2015).

Download citation

  • Published:

  • DOI: