Characterization of a common susceptibility locus for asthma-related traits.
Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein-coupled receptor named GPRA (G protein-coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism-tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.
Laitinen
Tarja
T
GeneOS Limited, 00251 Helsinki, Finland.
Polvi
Anne
A
Rydman
Pia
P
Vendelin
Johanna
J
Pulkkinen
Ville
V
Salmikangas
Paula
P
Mäkelä
Siru
S
Rehn
Marko
M
Pirskanen
Asta
A
Rautanen
Anna
A
Zucchelli
Marco
M
Gullstén
Harriet
H
Leino
Marina
M
Alenius
Harri
H
Petäys
Tuula
T
Haahtela
Tari
T
Laitinen
Annika
A
Laprise
Catherine
C
Hudson
Thomas J
TJ
Laitinen
Lauri A
LA
Kere
Juha
J
D000465:Algorithms; D017398:Alternative Splicing; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D001980:Bronchi / Q000737:chemistry / Q000166:cytology; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004847:Epithelial Cells / Q000737:chemistry; D005260:Female; D005387:Finland; D015870:Gene Expression; D005796:Genes; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000235:genetics; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000737:chemistry; D020641:Polymorphism, Single Nucleotide; D011792:Quebec; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000235:genetics*
C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; D007073:Immunoglobulin E