Characterization of a Common Susceptibility Locus for Asthma-Related Traits-Reference-Cited by-同舟云学术

Characterization of a Common Susceptibility Locus for Asthma-Related Traits

Published:2004-04-09 Issue:5668 Volume:304 Page:300-304
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Laitinen Tarja¹²³⁴⁵,Polvi Anne¹²³⁴⁵,Rydman Pia¹²³⁴⁵,Vendelin Johanna¹²³⁴⁵,Pulkkinen Ville¹²³⁴⁵,Salmikangas Paula¹²³⁴⁵,Mäkelä Siru¹²³⁴⁵,Rehn Marko¹²³⁴⁵,Pirskanen Asta¹²³⁴⁵,Rautanen Anna¹²³⁴⁵,Zucchelli Marco¹²³⁴⁵,Gullstén Harriet¹²³⁴⁵,Leino Marina¹²³⁴⁵,Alenius Harri¹²³⁴⁵,Petäys Tuula¹²³⁴⁵,Haahtela Tari¹²³⁴⁵,Laitinen Annika¹²³⁴⁵,Laprise Catherine¹²³⁴⁵,Hudson Thomas J.¹²³⁴⁵,Laitinen Lauri A.¹²³⁴⁵,Kere Juha¹²³⁴⁵

Affiliation:

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.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference16 articles.

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5. P. Höglundet al., Am. J. Hum. Genet.57, 95 (1995).

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