Publication Date:
2004-04-10
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laitinen, Tarja -- Polvi, Anne -- Rydman, Pia -- Vendelin, Johanna -- Pulkkinen, Ville -- Salmikangas, Paula -- Makela, Siru -- Rehn, Marko -- Pirskanen, Asta -- Rautanen, Anna -- Zucchelli, Marco -- Gullsten, Harriet -- Leino, Marina -- Alenius, Harri -- Petays, Tuula -- Haahtela, Tari -- Laitinen, Annika -- Laprise, Catherine -- Hudson, Thomas J -- Laitinen, Lauri A -- Kere, Juha -- New York, N.Y. -- Science. 2004 Apr 9;304(5668):300-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉GeneOS Limited, 00251 Helsinki, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15073379" target="_blank"〉PubMed〈/a〉
Keywords:
Algorithms
;
Alternative Splicing
;
Animals
;
Asthma/*genetics/metabolism
;
Bronchi/chemistry/cytology
;
Chromosomes, Human, Pair 7/*genetics
;
Epithelial Cells/chemistry
;
Female
;
Finland
;
Gene Expression
;
Genes
;
Genetic Linkage
;
*Genetic Predisposition to Disease
;
Genetic Variation
;
Genotype
;
*Haplotypes
;
Humans
;
Hypersensitivity/genetics/metabolism
;
Immunoglobulin E/blood
;
Inflammation/genetics
;
Lung/metabolism
;
Male
;
Mice
;
Myocytes, Smooth Muscle/chemistry
;
Polymorphism, Single Nucleotide
;
Quebec
;
Receptors, G-Protein-Coupled/analysis/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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