Host genetic susceptibility to subacute sclerosing panencephalitis (SSPE) in Japanese susceptibility

日本人对亚急性硬化性全脑炎（SSPE）的宿主遗传易感性

• 批准号: 14570607
• 负责人: KIRA Ryutaro
• 金额: $ 1.98万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570607/
• 关键词: subacute sclerosing panencephalitis; genetic polymorphism; measles virus; host; gene; MxA; disease susceptibility

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.

背景：MxA蛋白是由干扰素（IFN）α/β诱导产生的具有抗病毒活性的蛋白，可抑制包括麻疹病毒（MV）在内的单链RNA病毒的复制。我们研究了MxA基因是否与日本人亚急性硬化性全脑炎（SSPE）的发生有关。方法：我们筛选了MxA基因启动子区的单核苷酸多态性（SNP），进行了两个SNP与SSPE之间的关联研究，然后通过双荧光素酶报告基因分析研究了两个SNP启动子活性的功能差异。-88 G/T、-123 C/A、-200 T/C和-213 G/T，SSPE患者表现出比对照组更高的-88 T等位基因和-88 TT基因型频率（p=0.040和0.003）。IFN-诱导的MxA启动子活性的上调与-88 T序列被发现是显着高于与G。结论：这项研究已经证明了MxA启动子-88 G/T SNP赋予宿主对SSPE的遗传易感性的可能性在日本：MxA-88 T等位基因的纯合子与高MxA-88 T等位基因的发现，在SSPE患者中更常见的MxA蛋白产生能力似乎与MxA蛋白促进持续MV感染建立的假设相一致的神经细胞。

项目成果

Inoue T, Kira R, Nakao F, Ihara K, Bassuny WM, Kusuhara K, Nihei K, Takeshita K, Hara T: "Contribution of the interleukin 4 gene to susceptibility to subacute sclerosing panencephalitis."Arch Neurol. 59. 822-827 (2002)

Inoue T、Kira R、Nakao F、Ihara K、Bassuny WM、Kusuhara K、Nihei K、Takeshita K、Hara T：“白细胞介素 4 基因对亚急性硬化性全脑炎易感性的贡献。”Arch Neurol。

Tokunaga Y, Kira R, Takahata Y, Gondo K, Mizuno Y, Aoki T, Hara T: "Neurotrophin-4 and glial cell line-derived neurotrophic factor in cerebrospinal fluid from meningitis/encephalitis patients."Pediatr Neurol. 27. 102-105 (2002)

Tokunaga Y、Kira R、Takahata Y、Gondo K、Mizuno Y、Aoki T、Hara T：“脑膜炎/脑炎患者脑脊液中的神经营养蛋白-4 和神经胶质细胞系衍生的神经营养因子。”Pediatr Neurol。

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Torisu H, Kusuhara K, Kira R, Bassuny WM, Sakai Y, Sanefuji M, Takemoto M, Hara T: "Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis."Neurology. 62. 457-460 (2004)

Torisu H、Kusuhara K、Kira R、Bassuny WM、Sakai Y、Sanefuji M、Takemoto M、Hara T：“与亚急性硬化性全脑炎相关的功能性 MxA 启动子多态性。”神经病学。

Torisu H, Hara T: "subacute sclerosing panencephalitis and apoptosis."Jpn J Pediatr Med. 34(in Japanese). 101-104 (2002)

Torisu H，Hara T：“亚急性硬化性全脑炎和细胞凋亡。”Jpn J Pediatr Med。