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

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。

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.