| Project/Area Number |
20590735
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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 |
Gastroenterology
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| Research Institution | Tohoku University |
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Principal Investigator |
KINOUCHI Yoshitaka Tohoku University, 高等教育開発推進センター, 准教授 (20250780)
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| Co-Investigator(Kenkyū-buntansha) |
KAKUTA Yoichi 東北大学, 医学系研究科, 非常勤講師 (50509205)
根来 健一 東北大学, 病院, 医員 (50375028)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | クローン病 / 感受性遺伝子 / TNFSF15 / allelic expression imbalance / 感受性遺云子 |
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| Research Abstract |
TNFSF15 is a susceptibility gene for Crohn's disease (CD). We speculated that one or more of the SNPs associated with CD may act as cis-regulatory SNPs. To reveal the effects of the SNPs on the transcriptional activity of TNFSF15, we first examined the allelic expression imbalance of TNFSF15 in peripheral blood mononuclear cells (PBMCs). When PBMCs stimulated by phytohemagglutinin (PHA) were examined, the allelic ratio of mRNA transcribed from the risk haplotype to the non-risk haplotype increased, compared with the ratio without stimulation. When peripheral blood T cells and Jurkat cells stimulated by phorbol 12-myristate 13-acetate + ionomycin were examined, an allelic expression imbalance similar to that observed in PBMCs stimulated by PHA was confirmed. The promoter assay in stimulated Jurkat cells showed that the luciferase activity of the promoter region (-979 to +35) of the risk haplotype was significantly higher than that of the non-risk haplotype, and deletion and mutagenesis analysis demonstrated that this difference resulted from the -358T/C SNP. The promoter activity of -358C (risk allele) was higher than that of -358T (non-risk allele) in stimulated T cells. This effect of -358T/C on the transcriptional activity in stimulated T cells may confer susceptibility to CD.
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