title: Genetic predisposing factors to bronchopulmonary dysplasia: preliminary data from a multicentre study.
abstract: Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in preterm newborn infants. It is a multifactorial disease caused by the interaction between environmental and genetic factors. The aim of this study is to identify genetic variants contributing to BPD development using next-generation sequencing (NGS) technology. We prospectively evaluated 378 premature newborn infants with a gestational age <32 weeks in a multicentre study from 12 Italian neonatal intensive care unit from 2009 to 2012. Infants were divided into two groups: normal controls (225) and BPD-affected infants (141) with mild (65, 46.1%), moderate (40, 28.4%) and severe (36, 25.5%) BPD. BPD was more frequent in infants with lower weight and gestational age. Antenatal steroid administration was more frequent in the control group. Postnatal infection, respiratory distress syndrome, patent ductus arterious, cerebral haemorrhage, surfactant administration, ventilatory support, diuretics and postnatal steroid administration correlated with severity of BPD. Among BPD, moderate and severe cases will be selected as BPD "extreme phenotypes", and in fact variations in 28-day oxygen need-based BPD were previously shown to be fully attributable to environmental effects whereas dependence on supplemental oxygen at 36 weeks seems to better reflect underlying genetic susceptibility. Exome analysis by NGS is in progress. Identifications of genetic markers predisposing to BPD may allow development of personalized and preventive treatments.
authors.affiliation: Genomic Unit for Diagnosis of Human Pathologies, Center for Translational Genomics and Bioinformatics, Ospedale San Raffaele, Milan, Italy. masomaschini@gmail.com
authors.forename: Marco
authors.initials: M
authors.lastname: Somaschini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Castiglioni
authors.forename: Chiara
authors.initials: C
authors.lastname: Volonteri
authors.forename: Marco
authors.initials: M
authors.lastname: Cursi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ferrari
authors.forename: Paola
authors.initials: P
authors.lastname: Carrera
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001724:Birth Weight / Q000502:physiology; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011663:Pulmonary Surfactants / Q000378:metabolism; D012307:Risk Factors
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D011663:Pulmonary Surfactants