Hedgehog signaling pathway gene variant influences bronchopulmonary dysplasia in extremely low birth weight infants.
Gene
Infants
Lung
Preterm
Single nucleotide polymorphism
Journal
World journal of pediatrics : WJP
ISSN: 1867-0687
Titre abrégé: World J Pediatr
Pays: Switzerland
ID NLM: 101278599
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
14
12
2020
accepted:
22
03
2021
pubmed:
17
4
2021
medline:
15
12
2021
entrez:
16
4
2021
Statut:
ppublish
Résumé
Genome wide association study identified hedgehog interacting protein gene (HHIP) variants with chronic obstructive pulmonary disease and asthma. Loss of HHIP, a key regulator of the hedgehog signaling pathway, leads to impaired lung morphogenesis and lethality in animal models, through unimpeded sonic hedgehog expression blocking mesenchymal-expressed fibroblast growth factor 10 (FGF10). Since bronchopulmonary dysplasia (BPD) is also associated with altered lung development and worsens with stimuli including mechanical ventilation, reactive oxygen species, and inflammation, HHIP and FGF10 may be candidate genes. This was an observational, cohort study including extremely low birth weight infants that who developed BPD and those who did not. DNA was isolated from buccal swabs and subjected to allelic discrimination, using specific HHIP and FGF10 probes. Protein levels were measured in tracheal aspirates. Student's t test, Chi-square, Z test and logistic regression were used. Demographic characteristics did not differ except that birth weight (715 ± 153 vs. 835 ± 132 g) and gestational age (25 vs. 26 weeks) were less in babies with BPD. HHIP variant rs13147758 (GG genotype) was found to be independently protective for BPD (odds ratio 0.35, 95% confidence interval 0.15-0.82, P = - 0.02). Early airway HHIP protein levels were increased in infants with BPD compared to those without [median (interquartile range) 130.6 (55.6-297.0) and 41.2 (22.1-145.6) pg/mL, respectively; P = 0.05]. The FGF10 single nucleotide polymorphisms were not associated with BPD. HHIP, as a regulator of lung bud formation, affects BPD susceptibility, and may be valuable in understanding the specific mechanisms for this disease as well as for identifying therapeutic targets in the era of personalized medicine.
Sections du résumé
BACKGROUND
BACKGROUND
Genome wide association study identified hedgehog interacting protein gene (HHIP) variants with chronic obstructive pulmonary disease and asthma. Loss of HHIP, a key regulator of the hedgehog signaling pathway, leads to impaired lung morphogenesis and lethality in animal models, through unimpeded sonic hedgehog expression blocking mesenchymal-expressed fibroblast growth factor 10 (FGF10). Since bronchopulmonary dysplasia (BPD) is also associated with altered lung development and worsens with stimuli including mechanical ventilation, reactive oxygen species, and inflammation, HHIP and FGF10 may be candidate genes.
METHODS
METHODS
This was an observational, cohort study including extremely low birth weight infants that who developed BPD and those who did not. DNA was isolated from buccal swabs and subjected to allelic discrimination, using specific HHIP and FGF10 probes. Protein levels were measured in tracheal aspirates. Student's t test, Chi-square, Z test and logistic regression were used.
RESULTS
RESULTS
Demographic characteristics did not differ except that birth weight (715 ± 153 vs. 835 ± 132 g) and gestational age (25 vs. 26 weeks) were less in babies with BPD. HHIP variant rs13147758 (GG genotype) was found to be independently protective for BPD (odds ratio 0.35, 95% confidence interval 0.15-0.82, P = - 0.02). Early airway HHIP protein levels were increased in infants with BPD compared to those without [median (interquartile range) 130.6 (55.6-297.0) and 41.2 (22.1-145.6) pg/mL, respectively; P = 0.05]. The FGF10 single nucleotide polymorphisms were not associated with BPD.
CONCLUSION
CONCLUSIONS
HHIP, as a regulator of lung bud formation, affects BPD susceptibility, and may be valuable in understanding the specific mechanisms for this disease as well as for identifying therapeutic targets in the era of personalized medicine.
Identifiants
pubmed: 33860472
doi: 10.1007/s12519-021-00427-y
pii: 10.1007/s12519-021-00427-y
doi:
Substances chimiques
Hedgehog Proteins
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
298-304Références
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