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

点击翻译按钮获取中文摘要

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.