Skip to Main content Skip to Navigation
Journal articles

Identification of SPOCK2 as a susceptibility gene for bronchopulmonary dysplasia.: Genome-wide analysis of bronchopulmonary dysplasia

Abstract : RATIONALE: Bronchopulmonary dysplasia is the most common chronic respiratory disease in premature infants. Genetic factors might contribute to bronchopulmonary dysplasia susceptibility. OBJECTIVES: To identify genetic variants involved in bronchopulmonary dysplasia through a genome-wide association study. METHODS: We prospectively evaluated 418 premature neonates (gestational age <28 wk), of whom 22% developed bronchopulmonary dysplasia. Two discovery series were created, using a DNA pooling strategy in neonates from white and African ancestry. Polymorphisms associated with the disease were confirmed in an independent replication population. Genes were then explored by fine mapping and associations were replicated in an external Finnish population of 213 neonates. Validated genes expression patterns were studied in rat lung, after air or hyperoxia exposure. MEASUREMENTS AND MAIN RESULTS: SPOCK2 gene was identified by both discovery series. The most significant polymorphism (rs1245560; P = 1.66 × 10(-7)) was confirmed by individual genotyping, and in the replication population (P = 0.002). Fine mapping confirmed the association of rs1245560 with bronchopulmonary dysplasia in both white and African populations with adjusted odds ratios of 2.96 (95% confidence interval [CI], 1.37-6.40) and 4.87 (95% CI, 1.88-12.63), respectively. In white neonates, rs1049269 was also associated with the disease (odds ratio, 3.21; 95% CI, 1.51-6.82). These associations were replicated in the Finnish population. In newborn rat lungs, SPOCK2 mRNA levels markedly increased during the alveolar stage of lung development. After rat exposure to hyperoxia, SPOCK2 expression increased relative to air-exposed controls. CONCLUSIONS: We identified SPOCK2 as a new possible candidate susceptibility gene for bronchopulmonary dysplasia. Its lung expression pattern points toward a potential role in alveolarization.
Document type :
Journal articles
Complete list of metadatas

Cited literature [28 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00617002
Contributor : Georges Guellaen <>
Submitted on : Thursday, August 25, 2011 - 1:43:06 PM
Last modification on : Friday, October 16, 2020 - 3:21:45 AM
Long-term archiving on: : Sunday, December 4, 2016 - 6:02:21 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Citation

Alice Hadchouel, Xavier Durrmeyer, Emmanuelle Bouzigon, Roberto Incitti, Johanna Huusko, et al.. Identification of SPOCK2 as a susceptibility gene for bronchopulmonary dysplasia.: Genome-wide analysis of bronchopulmonary dysplasia. American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, 2011, 184 (10), pp.1164-70. ⟨10.1164/rccm.201103-0548OC⟩. ⟨inserm-00617002⟩

Share

Metrics

Record views

494