| Project/Area Number |
14570415
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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 |
内科学一般
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
TSUKAINOTO Hiroshi KYUSHU UNIVERSITY, University Hospital, Research Associate, 大学病院, 助手 (70304772)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Takahiko KYUSHU UNIVERSITY, University Hospital, Assistant Professor, 大学病院, 講師 (90219212)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Systemic lupus erythematosus / Rheumatoid arthritis / genetic analysis / single nucleotide polymorphisims / TNF family / cytokine / 一塩基多型(SNP) / B細胞 / 自己免疫疾患 / 慢性関節リウマチ / APRIL / BAFF / 遺伝子多型 / 疾患感受性遺伝子 |
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| Research Abstract |
Objective. To investigate the association of the gene polymorphisms in APRIL and BAFF, new members of the TNF family, with systemic lupus erythematosus(SLE)
Results. The human APRIL gene comprised at least six exons with five introns spanning approximately 2.4 kb of the genomic DNA. By exon-specific PCR/SSCP, we identified two novel polymorphisms at codons 67 and 96 Both had amino acid substitutions, G67R and N96S, respectively. Only the 67G allele was associated with SLE in 148 Japanese SLE patients with allele frequency 0.662 compared with 0.575 for 146 healthy controls (p=0.0302) The frequency of the individuals who possessed at least one 67G allele in SLE patients (91.9%) was significantly higher than that in normal controls (80.1%) (p=0.0036). There were no associations between the polymorphisms in BAFF gene and SLE. We developed ELISA for APRIL and BAFF, and demonstrated that serum levels of APRIL and BAFF were elevated in patients with SLE compared with healthy controls.
Conclusion. These results suggest that the 67G allele of APRIL is a contributing factor in the pathogenesis of SLE. The elevated serum levels of APRIL and BAFF may be associated with the pathogenesis of SLE.
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