| Project/Area Number |
16591069
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | RIKEN |
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Principal Investigator |
ONOUCHI Yoshihiro RIKEN, Laboratory for Gastrointestinal Diseases, Senior Scientist, 消化器系疾患関連遺伝子研究チーム, 上級研究員 (30360522)
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| Co-Investigator(Kenkyū-buntansha) |
SAJI Tsutomu Toho University school of medicine, Department of Pediatrics, Professor, 医学部・小児科学第一講座, 教授 (50120275)
KISHI Fumio Kagoshima University Dental School, Department of Microbiology and Immunology, Professor, 大学院・医歯学総合研究科, 教授 (40153077)
OUCHI Kazunobu Kawasaki Medical School, Dep. of Pediatrics, Professor, 医学部, 教授 (80351899)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Kawasaki disease / susceptibility gene / SNP / 罹患同胞対解析 / CD40 ligand / 冠動脈病変 |
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| Research Abstract |
To identify susceptibility gene for Kawasaki disease (KD), we applied linkage disequilibrium mapping method to chromosomal regions in which positive linkage signals have been observed in our previous study. As a result of case control study using 637 KD patients and 1034 control samples, we identified a single nucleotide polymorphism (SNP) which was significantly associated with KD (OR 1.89, 95%CI 1.53-2.33, x^2=35.8, p=2.2x10^9). The positive association was replicated in an analysis of 209 KD samples of the U.S. by transmission disequilibrium test (OR 2.13, 95%CI 1.38-3.29, x^2=12.3, p=0.00045). Furthermore, the SNP was associated with increased risk of coronary artery lesions and resistance to intravenous immunoglobulin therapy.
The SNP is located within intron 1 of a gene on chromosome 19 (gene X). Expression of the gene X is highly induced in PBMCs after stimulation with PHA and PMA. Knockdown and over-expression of the gene in Jurkat cells resulted in increased and decreased expression of IL-2 in the cells respectively.
Allele specific transcript quantification method revealed the reduced amount of the gene X transcript from the risk allele compared with the no-risk allele in PBMCs from healthy donors heterozygous about the SNP
Thus, the gene product was speculated to act as a negative regulator of T-cells and the SNP may contribute to immune hyper-reactivity in KD.
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