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Science 304 (5668): 300-304

Copyright © 2004 by the American Association for the Advancement of Science

Characterization of a Common Susceptibility Locus for Asthma-Related Traits

Tarja Laitinen,1,2 Anne Polvi,2 Pia Rydman,1 Johanna Vendelin,1,2 Ville Pulkkinen,1 Paula Salmikangas,1 Siru Mäkelä,2 Marko Rehn,1 Asta Pirskanen,1 Anna Rautanen,4 Marco Zucchelli,5 Harriet Gullstén,2,5 Marina Leino,6 Harri Alenius,6 Tuula Petäys,7 Tari Haahtela,7 Annika Laitinen,3 Catherine Laprise,9 Thomas J. Hudson,10 Lauri A. Laitinen,8 Juha Kere*2,5

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.

1 GeneOS Limited, 00251 Helsinki, Finland.
2 Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
3 Department of Anatomy, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
4 Finnish Genome Center, University of Helsinki, 00014 Helsinki, Finland.
5 Department of Biosciences at Novum and Clinical Research Centre, Karolinska Institutet, 14157 Huddinge, Sweden.
6 Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, 00251 Helsinki, Finland.
7 Department of Allergological Diseases, Helsinki University Central Hospital, 00029 Helsinki, Finland.
8 Department of Medicine, Helsinki University Central Hospital, 00029 Helsinki, Finland.
9 Community Genomic Medicine Centre, Université du Québec à Chicoutimi, Saguenay, Quebec G7H 2B1 Canada.
10 McGill University and Genome Quebec Innovation Centre, Montreal, Quebec H3A 1A4 Canada.

* To whom correspondence should be addressed. E-mail: juha.kere{at}biosci.ki.se


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