Abstract | BACKGROUND: OBJECTIVES: METHODS: We performed a genome-wide association study with 60 patients and 300 control subjects. We applied stringent filter and visual assessments for selecting single nucleotide polymorphisms (SNPs) and a high false discovery rate threshold. We fine-mapped the region where a candidate SNP was found and confirmed the results by means of sequencing. We evaluated the function of agonist-activated prostaglandin E receptor 3 (EP3), the gene for which contained several SNPs, in regulating cytokine production in human conjunctival epithelial (CE) cells. The expression levels of EP3 in the CE cells from patients and control subjects were also compared. RESULTS: We identified 3 SNPs that passed the false discovery rate threshold. One (rs17131450) was close to the EP3 gene. Therefore we analyzed the EP3 region in detail and identified 5 other SNPs. We confirmed the association between SJS/TEN and all 6 SNPs. Activated EP3 was expressed in control CE cells, and it suppressed polyI:C-stimulated cytokine production, suggesting that EP3 might help prevent ocular surface inflammation. Concordantly, the EP3 levels were much lower in the CE cells of the patients than in those of the control subjects. CONCLUSION: We demonstrated, using both genetic and functional analyses, that EP3 could be a key player in the pathogenesis of SJS/TEN accompanied by ocular complications.
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Authors | Mayumi Ueta, Chie Sotozono, Masakazu Nakano, Takazumi Taniguchi, Tomohito Yagi, Yuichi Tokuda, Masahiro Fuwa, Tsutomu Inatomi, Norihiko Yokoi, Kei Tashiro, Shigeru Kinoshita |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 126
Issue 6
Pg. 1218-25.e10
(Dec 2010)
ISSN: 1097-6825 [Electronic] United States |
PMID | 20947153
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Cytokines
- ONO AE 248
- Receptors, Prostaglandin E, EP3 Subtype
- Dinoprostone
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Topics |
- Cell Line
- Conjunctiva
(pathology)
- Cytokines
(genetics, metabolism)
- DNA Mutational Analysis
- Dinoprostone
(analogs & derivatives, pharmacology)
- Epithelial Cells
(drug effects, metabolism, pathology)
- Gene Frequency
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Genotype
- Humans
- Inflammation
- Polymorphism, Genetic
- Receptors, Prostaglandin E, EP3 Subtype
(agonists, genetics)
- Stevens-Johnson Syndrome
(genetics, pathology, physiopathology)
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