Summary of Research Project Results under JSPS FY2004
"Research for the Future Program"


1. Research Institution   The University of Tokyo
2. Research Area Life Sciences
3. Research Field Genome Research
4. Term of Project FY 2000 - FY 2004
5. Project Number 00L01401
6. Title of Project Systematic Genetic Study of Asthma and Atopic Dermatitis Based on the Genome-Wide SNP Informatics

7. Project Leader

Name Institution, Department Title of Position
Ituro, Inoue The University of Tokyo,Institute of Medical Science Associate Professor

8. Core Members

Names Institution, Department Title of Position
Yoshinori, Hasegawa Nagoya University, School of Medicine Lecturer

9. Summary of Research Results

Bronchial asthma (BA), one of the most common of all chronic inflammatory diseases in human populations, is resulted from a combination of environmental and genetic factors. One approach to address the genetic factors associated with BA is to undertake extensive surveys of candidate genes to search for variations, and to test allelic association studies. We selected genes as candidates that may relate to inflammation or apoptosis, such as genes encoding proteins related to cell-cell interactions (cytokines and their receptors) and those involved in the arachidonic acid cascade. These products are well known to have various biological activities and some have been shown to induce inflammation. The differences in response are likely to reflect subtle variations among genes encoding the proteins involved in this pathway. One of our interests is to identify susceptibility for aspirin-intolerant asthma (AIA). AIA is a distinct clinical syndrome characterized by adverse respiratory reactions to aspirin and other non-steroid anti-inflammatory drugs. Because of the pharmacological action of aspirin, candidate genes for AIA could be easily listed on arachidonic acid cascade. Accordingly, we screened 63 candidate genes in the pathway to identify the causality of AIA. Prostaglandin E2 receptor type 2 was identified as a susceptibility to AIA. The polymorphism in the promoter was strongly associated with AIA and the functioned as showing decreased transcriptional activity. Because of an anti-inflammatory action of PGE2, the decreased level of EP2 might result in dysfunction of the PGE2 anti-inflammatory action that constitutes the inherent causality of AIA.

10. Key Words

( 1 ) SNP ( 2 ) atopic asthma ( 3 ) aspirin-intolerant asthma
( 4 ) EP2 ( 5 ) linkage disequilibrium ( 6 ) haplotype
( 7 ) evolutional medicine ( 8 ) natural selection ( 9 ) permutation analysis

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