| Project/Area Number |
15591187
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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 |
Dermatology
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| Research Institution | Osaka City University Graduate School of Medicine |
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Principal Investigator |
FUKAI Kazuyoshi Osaka City University, Department of Dermatology, Associate professor, 大学院・医学研究科, 助教授 (20244642)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | IRF2 / polymorphism / promoter / psoriasis / 多因子遺伝 / 遺伝子多型 / 転写因子 / USF |
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| Research Abstract |
Interferon regulatory factor 2 (IRF-2) is a transcriptional regulatory protein which represses the expression of interferon-alpha/beta genes. In mice lacking IRF-2, the inflammatory skin disease very similar to human psoriasis develops spontaneously. In addition, IRF-2 gene is located at human chromosome 4q35, where a familial psoriasis susceptibility locus has been mapped. Therefore, we hypothesized the IRF-2 gene is a possible candidate gene for psoriasis.
Genotyping of -535G>A was performed by NlaIII-restriction flagment polymorphism (RFLP). Gel-shift and super-shift analysis were employed for the accessment of the binding abilities of transcription factors. To demonstrate differential transcriptional activities, luciferase reporter assays were perforemed.
We identified a -535G>A polymorphism in the IRF-2 transcriptional promoter. The -535A allele was more frequent (p= 0.035) in early-onset (less than 41 years of age) psoriasis in Japan, although this was not associated with the old-onset (41 years or older) psoriasis. The -535G allele was found to bind upstream stimulatory factor (USF) by the supershift analysis, whereas the -535A allele did not bind USF. However, the reporter assay revealed no statistical difference of the transcriptional activity between -535A allele and -535G allele. Furthermore, co-transfection of the USF-1 expression vector did not stimulate the promoter activity of our luciferase reporter system.
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