| Project/Area Number |
12204002
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
TOKUNAGA Katsushi The University of Tokyo, Graduate School of Mediche, Professor, 大学院医学系研究科, 教授 (40163977)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUCHIYA Naoyuki The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (60231437)
|
|---|
| Project Period (FY) |
2000 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥90,300,000 (Direct Cost: ¥90,300,000)
Fiscal Year 2004: ¥22,000,000 (Direct Cost: ¥22,000,000)
Fiscal Year 2003: ¥21,900,000 (Direct Cost: ¥21,900,000)
Fiscal Year 2002: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2001: ¥24,000,000 (Direct Cost: ¥24,000,000)
|
|---|
| Keywords | rheumatoid arthritis / systemic lupus erythematosus / Fc gamma receptor genes / CD72 / CD19 / TNF-TNF receptor family gene family / NK cell receptor genes / ID genes / CD72遺伝子 / 選択的スプライシング / FCGR2B遺伝子 / APRIL遺伝子 / 血管新生 / FCCR遺伝子群 / Blys遺伝子 / TACI遺伝子 / 細胞膜ラフト / 慢性関節リウマチ / Blys / FCGR遺伝子群 / 滑膜細胞 / SNP(単一塩基多型) / NKG2C / FCGR2B / FosB / SNP / 多型 / ID3 / 疾患感受性遺伝子 |
|---|
| Research Abstract |
Genome analyses of the patients with rheumatic and diffuse collagen diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were performed, and several genes were found to be associated with the diseases. These findings contribute to the elucidation of pathogenesis of these diseases. (1) Association between FCGR2B and SLE was detected. Susceptibility allele product showed a weaker inhibitory effect on B cell activation. (2) Association between CD72 and nephritis-positive SLE was detected. Resistant haplotype produced higher level of alternatively-spliced mRNA. (3) Several TNF and TNF receptor family genes were analyzed, and associations of BLyS and APRIL with SLE were detected. APRIL susceptibility allele produced higher level of mRNA and protein. (4) NK receptor genes including NKG2A, NKG2C and CD94 were not associated with RA nor SLE, but the frequency of NKG2C-deleted haplotype reached 20%. (5) Presence/absence polymorphism of KIR genes was shown to be associated with microscopic polyangitis. (6) Association of LILRB1 with HLA-DRB1 "shared epitope"-positive RA was detected. Susceptibility haplotype expressed lower level of the molecule. (7) A total of 20 genes were found to be up-regulated in RA synovium. in which ID genes were further subjected for in-vitro functional analyses. These genes were found to be essential for the activation of endothelial cells and angiogenesis.
|
