| Project/Area Number |
14370160
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YSUCHIYA Naoyuki The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (60231437)
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| Co-Investigator(Kenkyū-buntansha) |
HONDA Zen-ichiro The University of Tokyo, Hospital, Lecturer, 医学部附属病院, 講師 (70238814)
山口 晃弘 東京大学, 医学部附属病院, 助手 (90261974)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | systemic lupus erythematosus / rheumatoid arthritis / polymorphism / Fc_γ receptor IIb / CD72 / Id / LILR / APRIL / 顕微鏡的多発血管炎 / FCGR2B / LILRB1 / KIR / HLA / スプライシング / 遺伝子間相互作用 / 血管新生 / 強皮症 / CD19 / Fcγ受容体 / メタアナリシス / NK受容体 / 欠失 / 国際情報交換 / Fcγ受容体IIb / BLyS(BAFF) / ILT2(LIR1) / ID / 遺伝子発現 |
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| Research Abstract |
1.A SNP coding for an amino acid substitution within the transmembrane domain of an inhibitory receptor of B lymphocytes, FCGR2B Ile232Thr, was identified. The genotype 232Thr/Thr was significantly increased in systemic lupus erythematosus (SLE) in three Asian populations. Functional studies revealed that localization of 232Thr allele product in membrane lipid raft was decreased, and the inhibitory signals transmitted from the 232Thr product were weaker than those from the 232Ile product.
2.Two major haplotypes were identified in human CD72. One of the haplotypes was associated with increase of an alternative splicing isoform, in which extracellular region is substantially altered. This haplotype was associated with protection from nephritis in the patients with SLE. Moreover, the risk conferred by FCGR2B-232Thr was significantly decreased in the presence of this CD72haplotype through epistatic interaction.
3.A promoter SNP was identified to be associated with increased expression of CD1
… More
9 and susceptibility to systemic sclerosis.
4.A number of polymorphisms were identified in BLyS (BAFF), APRIL and their receptors, BAFF-R, TACI and BCMA. SNPs in APRIL were confirmed to be associated with susceptibility to SLE in Japanese.
5.A haplotype with NKG2C deletion was found to be commonly present in the Japanese and Dutch populations, with haplotype frequencies of 20.2% and 20.0%, respectively. Homozygous deficiency was found in 4.1% and 3.8% in the Japanese and Dutch general populations, suggesting that NKG2C is not essential for survival or reproduction.
6.LILRB1 (ILT2, LIR1) was found to be highly polymorphic, and one of the haplotypes was associated with susceptibility to rheumatoid arthritis (RA) in HLA-DRB1 shared epitope negative individuals.
7.Association of HLA-DRB1^*0901-DQB1^*0303 haplotype and KIR genotypes with Japanese patients with microscopic polyangiitis was demonstrated.
8.Id genes were overexpressed in the endothelial cells within RA synovial tissues. Id was found to be essential for the induction of endothelial cell activation and angiogenic properties by VEGF in human umbilical vein endothelial cells. Less
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