title: Characterization of a common susceptibility locus for asthma-related traits.
abstract: 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.
authors.affiliation: GeneOS Limited, 00251 Helsinki, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Laitinen
authors.forename: Anne
authors.initials: A
authors.lastname: Polvi
authors.forename: Pia
authors.initials: P
authors.lastname: Rydman
authors.forename: Johanna
authors.initials: J
authors.lastname: Vendelin
authors.forename: Ville
authors.initials: V
authors.lastname: Pulkkinen
authors.forename: Paula
authors.initials: P
authors.lastname: Salmikangas
authors.forename: Siru
authors.initials: S
authors.lastname: Mäkelä
authors.forename: Marko
authors.initials: M
authors.lastname: Rehn
authors.forename: Asta
authors.initials: A
authors.lastname: Pirskanen
authors.forename: Anna
authors.initials: A
authors.lastname: Rautanen
authors.forename: Marco
authors.initials: M
authors.lastname: Zucchelli
authors.forename: Harriet
authors.initials: H
authors.lastname: Gullstén
authors.forename: Marina
authors.initials: M
authors.lastname: Leino
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Tuula
authors.initials: T
authors.lastname: Petäys
authors.forename: Tari
authors.initials: T
authors.lastname: Haahtela
authors.forename: Annika
authors.initials: A
authors.lastname: Laitinen
authors.forename: Catherine
authors.initials: C
authors.lastname: Laprise
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Laitinen
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
mesh_terms: 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*
chemical_list: C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; D007073:Immunoglobulin E