title: ATP-binding cassette member A3 (E292V) gene mutation and pulmonary morbidity in very-low-birth-weight infants.
abstract: OBJECTIVE
  ATP-binding cassette member A 3 (ABCA3) plays a critical role for the transport of surfactant phospholipids into the lamellar bodies of type II alveolar epithelial cells. Term infants carrying the E292V missense mutation of the gene encoding ABCA3 are likely to develop respiratory distress syndrome, and the mutation has also been linked to interstitial lung disease in paediatric patients. The aim of this study was to investigate the association of the E292V genotype with pulmonary morbidity in a large cohort of very-low-birth-weight (VLBW) infants.
  
  
  METHODS
  We performed a genetic association study with a prospective, population-based multi-centre cohort of 3177 VLBW infants born in 16 German study centres between 2003 and 2009 (German Neonatal Network). The ABCA3 genotype was determined by restriction fragment length polymorphism-PCR in genomic DNA samples derived from buccal swabs.
  
  
  RESULTS
  In a large cohort of 3177 VLBW infants, 11 individuals were found to be heterozygote for the E292V mutation (0.34%). After stratification according to ABCA3 genotype, no differences were noted for clinical characteristics, necessary treatments and neonatal pulmonary outcomes.
  
  
  CONCLUSIONS
  Within the size limits of our study cohort, the ABCA3 missense mutation E292V had no remarkable effect on pulmonary outcome in VLBW infants. Present results do not rule out the possibility that E292V phenotype is associated with minor difference in the morbidity.
authors.affiliation: Department of Pediatrics, University at Lübeck, Lübeck, Germany. haertel@paedia.ukl.mu-luebeck.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Härtel
authors.forename: Ursula
authors.initials: U
authors.lastname: Felderhoff-Müser
authors.forename: Corinna
authors.initials: C
authors.lastname: Gebauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoehn
authors.forename: Angela
authors.initials: A
authors.lastname: Kribs
authors.forename: Reinhard
authors.initials: R
authors.lastname: Laux
authors.forename: Jens
authors.initials: J
authors.lastname: Möller
authors.forename: Hugo
authors.initials: H
authors.lastname: Segerer
authors.forename: Norbert
authors.initials: N
authors.lastname: Teig
authors.forename: Axel
authors.initials: A
authors.lastname: von der Wense
authors.forename: Christian
authors.initials: C
authors.lastname: Wieg
authors.forename: Guido
authors.initials: G
authors.lastname: Stichtenoth
authors.forename: Egbert
authors.initials: E
authors.lastname: Herting
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Göpel
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D017563:Lung Diseases, Interstitial / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009017:Morbidity; D020125:Mutation, Missense; D011446:Prospective Studies; D012127:Respiratory Distress Syndrome, Newborn / Q000453:epidemiology / Q000235:genetics*
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters