G protein-coupled receptor for asthma susceptibility associates with respiratory distress syndrome.
BACKGROUND
Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) have some common features with asthma.


OBJECTIVE
To study whether G protein-coupled receptor for asthma susceptibility (GPRA) contributes to RDS or BPD.


METHODS
A haplotype association study was performed in a case-control setting of 521 Finnish infants (including 176 preterm neonates with RDS and 37 with BPD). Immunoreactivity of GPRA isoforms A and B was determined in pulmonary samples of fetuses, term infants and preterm infants with RDS or BPD. GPRA mRNA expression was determined by quantitative real-time polymerase chain reaction (PCR) in samples from nasal respiratory epithelium of adults, term infants and preterm infants.


RESULTS
In infants with RDS born at 32-35 weeks of gestation, GPRA haplotype H1 was significantly underrepresented in RDS, whereas haplotype H4/H5 was associated with an increased risk. As in asthma, GPRA B isoform was induced in bronchial smooth muscle cells in RDS and BPD. In nasal respiratory epithelium, relative GPRA mRNA expression was strong in adults, weak in preterm and slightly higher in term samples.


CONCLUSIONS
The results suggest that near-term RDS and asthma share the same susceptibility and protective GPRA haplotypes. Altered GPRA expression may play a role in the pathogenesis of RDS and BPD in preterm infants.
Pulkkinen
Ville
V
Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland. ville.pulkkinen@helsinki.fi
Haataja
Ritva
R
Hannelius
Ulf
U
Helve
Otto
O
Pitkänen
Olli M
OM
Karikoski
Riitta
R
Rehn
Marko
M
Marttila
Riitta
R
Lindgren
Cecilia M
CM
Hästbacka
Johanna
J
Andersson
Sture
S
Kere
Juha
J
Hallman
Mikko
M
Laitinen
Tarja
T
D000328:Adult; D001249:Asthma / Q000209:etiology* / Q000235:genetics; D001483:Base Sequence; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D012307:Risk Factors
C484532:NPSR1 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled