title: Data mining and multiparameter analysis of lung surfactant protein genes in bronchopulmonary dysplasia.
abstract: Bronchopulmonary dysplasia (BPD), the most common chronic lung disease in infancy, is influenced by a number of antenatal and postnatal risk factors and is mostly preceded by respiratory distress syndrome (RDS) in the newborn. Surfactant protein (SP-A, -B, -C and -D) gene variations may play a role in both BPD and RDS. An association study between these candidate genes and BPD was performed. A total of 365 preterm Finnish infants in a high-risk population with gestational age <or=32 weeks were genotyped for all SP genes. A multiparameter analysis was performed using Agrawal's algorithm based data mining and conventional methods of statistical allelic association. In singletons and presenting multiples, the frequency of SP-B intron 4 deletion variant allele was increased in BPD versus controls (P=0.008, OR=2.0, 95%CI 1.2-3.4). The presence of the SP-B intron 4 deletion variant was a risk factor for BPD even when essential external confounding factors were included in the analyses. No other SP polymorphisms associated with BPD, and the SP-B intron 4 variation did not associate with RDS. Transcription Element Search Software predicted allele-specific differences at several putative transcription factor binding sites that may be important in SP-B regulation. The present multiparameter analysis demonstrates the presumable direct involvement of the SP-B intron 4 deletion variant allele as a genetic risk factor to BPD. We propose that two separate SP-B gene polymorphisms have a phenotypic significance via separate molecular mechanisms: the intron 4 length variation affecting transcriptional regulation, and the exonic Ile131Thr variation affecting post-translationally.
authors.affiliation: Department of Paediatrics and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Meri
authors.initials: M
authors.lastname: Rova
authors.forename: Ritva
authors.initials: R
authors.lastname: Haataja
authors.forename: Riitta
authors.initials: R
authors.lastname: Marttila
authors.forename: Vesa
authors.initials: V
authors.lastname: Ollikainen
authors.forename: Outi
authors.initials: O
authors.lastname: Tammela
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000235:genetics*; D016022:Case-Control Studies; D019295:Computational Biology; D016172:DNA Fingerprinting; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011153:Population / Q000235:genetics; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D037661:Pulmonary Surfactant-Associated Proteins; D014157:Transcription Factors