Abstract
Aim
Genetic variants contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study is to evaluate the association of 45 SNPs with BPD susceptibility in a Turkish premature infant cohort.
Methods
Infants with gestational age <32 weeks were included. Patients were divided into BPD or no-BPD groups according to oxygen need at 28 days of life, and stratified according to the severity of BPD. We genotyped 45 SNPs, previously identified as BPD risk factors, in 192 infants.
Results
A total of eight SNPs were associated with BPD risk at allele level, two of which (rs4883955 on KLF12 and rs9953270 on CHST9) were also associated at the genotype level. Functional relationship maps suggested an interaction between five of these genes, converging on WNT5A, a member of the WNT pathway known to be implicated in BPD pathogenesis. Dysfunctional CHST9 and KLF12 variants may contribute to BPD pathogenesis through an interaction with WNT5A.
Conclusions
We suggest investigating the role of SNPs on different genes which are in relation with the Wnt pathway in BPD pathogenesis. We identified eight SNPs as risk factors for BPD in this study. In-silico functional maps show an interaction of the genes harboring these SNPs with the WNT pathway, supporting its role in BPD pathogenesis.
Trial registration
NCT03467828.
Impact
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It is known that genetic factors may contribute to the development of BPD in preterm infants. Further studies are required to identify specific genes that play a role in the BPD pathway to evaluate them as a target for therapeutic interventions.
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Our study shows an association of BPD predisposition with certain polymorphisms on MBL2, NFKBIA, CEP170, MAGI2, and VEGFA genes at allele level and polymorphisms on CHST9 and KLF12 genes at both allele and genotype level.
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In-silico functional mapping shows a functional relationship of these five genes with WNT5A, suggesting that Wnt pathway disruption may play a role in BPD pathogenesis.
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Acknowledgements
This study was supported by a grant from the Scientific Research Project Programme of the Yıldız Technical University with a project number of 2016-07-04-DOP02.
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A.A.; conceptualization, methodology, acquisition of data, formal analysis and investigation, resources, and writing—original draft preparation, S.Y.S; conceptualization, methodology, acquisition of data, and writing—original draft preparation, O.M.U.; formal analysis and investigation, and resources, A.E.; formal analysis and investigation, and resources. M.C.; conceptualization, methodology, acquisition of data, and writing—review and editing. O.D.; writing—review, editing, and providing the final version of the manuscript. D.T.-B.; conceptualization, methodology, acquisition of data, formal analysis and investigation, resources, and writing—original draft preparation, funding, and supervision.
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The study was approved by the local Ethics Committee of Kanuni Sultan Suleyman Training and Research Hospital (KAEK/2016.12.31).
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Akat, A., Yilmaz Semerci, S., Ugurel, O.M. et al. Bronchopulmonary dysplasia and wnt pathway-associated single nucleotide polymorphisms. Pediatr Res 92, 888–898 (2022). https://doi.org/10.1038/s41390-021-01851-6
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DOI: https://doi.org/10.1038/s41390-021-01851-6
