Characterization of a Common Susceptibility Locus for Asthma-Related Traits

Tarja Laitinen(University of Helsinki), Anne Polvi(University of Helsinki), Pia S. Rydman(University of Helsinki), Johanna Vendelin(University of Helsinki), Ville Pulkkinen(University of Helsinki), Paula Salmikangas(University of Helsinki), Siru Mäkelä(University of Helsinki), Marko Rehn(University of Helsinki), Asta Pirskanen(University of Helsinki), Anna Rautanen(University of Helsinki), Marco Zucchelli(University of Helsinki), Harriet Gullstén(University of Helsinki), Marina Leino(University of Helsinki), Harri Alenius(University of Helsinki), Tuula Petäys(University of Helsinki), Tari Haahtela(University of Helsinki), Annika Laitinen(University of Helsinki), Catherine Laprise(University of Helsinki), Thomas J. Hudson(University of Helsinki), Lauri A. Laitinen(University of Helsinki), Juha Kere(University of Helsinki)
Science
April 8, 2004
10.1126/science.1090010
Cited by 486

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.

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