Characterization of a Common Susceptibility Locus for Asthma-Related Traits

• Published in: Science (American Association for the Advancement of Science) 2004-04, Vol.304 (5668), p.300-304
• Main Authors: Laitinen, Tarja, Polvi, Anne, Rydman, Pia, Vendelin, Johanna, Pulkkinen, Ville, Salmikangas, Paula, Mäkelä, Siru, Rehn, Marko, Pirskanen, Asta, Rautanen, Anna, Zucchelli, Marco, Gullstén, Harriet, Leino, Marina, Alenius, Harri, Petäys, Tuula, Haahtela, Tari, Laitinen, Annika, Laprise, Catherine, Hudson, Thomas J., Laitinen, Lauri A., Kere, Juha
• Format: Article
• Language: English
• Subjects: Algorithms; Allergic diseases; Alternative Splicing; Animals; Association Measures; Asthma; Asthma - genetics; Asthma - metabolism; Biological and medical sciences; Bronchi - chemistry; Bronchi - cytology; Causes of; Chromosomes; Chromosomes, Human, Pair 7 - genetics; Deoxyribonucleic acid; DNA; Epithelial cells; Epithelial Cells - chemistry; Exons; Female; Finland; French Canadians; Gene Expression; Gene loci; Genes; Genetic aspects; Genetic Linkage; Genetic loci; Genetic Predisposition to Disease; Genetic Variation; Genetics; Genomes; Genomics; Genotype; GPRA protein; Haplotypes; Humans; Hypersensitivity - genetics; Hypersensitivity - metabolism; Immunoglobulin E - blood; Immunopathology; Inflammation - genetics; Lung - metabolism; Male; Mathematics; Medical sciences; Medicin och hälsovetenskap; Mice; Myocytes, Smooth Muscle - chemistry; Patients; Polymorphism, Single Nucleotide; Protein isoforms; Quebec; Receptors, G-Protein-Coupled - analysis; Receptors, G-Protein-Coupled - genetics; Research universities; Respiratory and ent allergic diseases
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1090010

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.