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

背景：具有抗病毒活性的MxA蛋白由干扰素α/β诱导，可抑制包括麻疹病毒在内的单链病毒的复制。方法：在日本亚急性硬化性全脑炎(SSPE)患者中筛选MxA基因启动子区域的单核苷酸多态(SNPs)，研究两个SNPs与SSPE的关联性，并用双荧光素酶报告基因分析比较两个SNPs启动子活性的功能差异。结果：共发现4个SNPs：-88G/T、-123C/A、-200T/C和-213G/T。SSPE患者的-88T等位基因和-88TT基因频率均高于对照组(p=0.040和0.003)。结论：本研究证实了日本人MXA启动子-88G/T SNP使宿主对SSPE的遗传易感性的可能性：MXA-88T等位基因的纯合子在SSPE患者中更常见，这与MXA蛋白促进神经细胞持续MV感染的假设相一致。

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.