Characterization of a common susceptibility locus for asthma-related traits

被引：334

作者：

Laitinen, T

Polvi, A

Rydman, P

Vendelin, J

Pulkkinen, V

Salmikangas, P

Mäkelä, S

Rehn, M

Pirskanen, A

Rautanen, A

Zucchelli, M

Gullstén, H

Leino, M

Alenius, H

Petäys, T

Haahtela, T

Laitinen, A

Laprise, C

Hudson, TJ

Laitinen, LA

Kere, J ^{[1
]}

机构：

[1] Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland

[2] GeneOS Ltd, Helsinki 00251, Finland

[3] Univ Helsinki, Biomedicum, Dept Anat, FIN-00014 Helsinki, Finland

[4] Univ Helsinki, Finnish Genome Ctr, FIN-00014 Helsinki, Finland

[5] Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden

[6] Karolinska Inst, Clin Res Ctr, S-14157 Huddinge, Sweden

[7] Finnish Inst Occupat Hlth, Dept Ind Hyg & Toxicol, Helsinki 00251, Finland

[8] Univ Helsinki, Cent Hosp, Dept Allergol Dis, Helsinki 00029, Finland

[9] Univ Helsinki, Cent Hosp, Dept Med, Helsinki 00029, Finland

[10] Univ Quebec, Community Gen Med Ctr, Chicoutimi, PQ G7H 2B1, Canada

[11] McGill Univ, Montreal, PQ H3A 1A4, Canada

[12] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada

来源：

SCIENCE | 2004年 / 304卷 / 5668期

关键词：

D O I：

10.1126/science.1090010

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：300 / 304

页数：5

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