| Project/Area Number |
14570607
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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 |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
KIRA Ryutaro Kyushu University, Graduate School of Medical Sciences, Assistant Prof, 大学院・医学研究院, 助手 (70304805)
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| Co-Investigator(Kenkyū-buntansha) |
TORISU Hiroyuki Kyushu University, Graduate School of Medical Sciences, Medical Staff, 大学病院, 医員
KUSUHARA Koichi Kyushu University, Graduate School of Medical Sciences, Assoc. Prof, 大学院・医学研究院, 助教授 (20243941)
HARA Toshiro Kyushu University, Graduate School of Medical Sciences, Prof, 大学院・医学研究院, 教授 (40150445)
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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 |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | subacute sclerosing panencephalitis / genetic polymorphism / measles virus / host / gene / MxA / disease susceptibility |
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| Research Abstract |
Background :
The antivirally active MxA protein is Induced by interferon (IFN) α/β and inhibits the replication of single-stranded RNA viruses including measles virus (MV). We investigated whether the MxA gene contributed to the development of subacute sclerosing panencephalitis (SSPE) In Japanese.
Methods :
We screened single nucleotide polymorphisms (SNPs) in the promoter region of the MxA gene, performed association studies between two SNPs and SSPE, and then investigated a functional difference in the promoter activities of the two SNPs by a dual luciferase reporter assay.
Results :
Four SNPs were found : -88 G/T, -123 C/A, -200 T/C and -213 G/T, and SSPE patients exhibited a higher frequency of both the -88T allele and the -88TT genotype than controls (p=0.040 and 0.003). The IFN-induced upregulation of the MxA promoter activity of the sequence with -88T was found to be significantly higher than that with G.
Conclusion :
This study has demonstrated the possibility that the MxA promoter -88 G/T SNP confers host genetic susceptibility to SSPE in Japanese: The finding that homozygotes of the MxA -88T allele with a high MxA-producing capability were more frequently seen in SSPE patients appears to be compatible with the hypothesis that the MxA protein promotes the establishment of persistent MV infection of neural cells.
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