Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis

H. Torisu, K. Kusuhara, R. Kira, W. M. Bassuny, Y. Sakai, M. Sanefuji, M. Takemoto, T. Hara

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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). The authors investigated whether the MxA gene contributed to the development of subacute sclerosing panencephalitis (SSPE) in Japanese individuals. Methods: Single-nucleotide polymorphisms (SNP) in the promoter region of the MxA gene were screened, association studies were performed between two SNP and SSPE, and then a functional difference in the promoter activities of the two SNP was investigated by a dual luciferase reporter assay. Results: Four SNP 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 up-regulation of the MxA promoter activity of the sequence with -88T was found to be significantly higher than that with G. Conclusions: MxA promoter -88 G/T SNP may confer host genetic susceptibility to SSPE in Japanese individuals. The finding that homozygotes of the MxA -88T allele with a high MxA-producing capability were more frequently seen in SSPE patients suggests that the MxA protein promotes the establishment of persistent MV infection of neural cells.

Original languageEnglish
Pages (from-to)457-460
Number of pages4
JournalNeurology
Volume62
Issue number3
DOIs
Publication statusPublished - Feb 10 2004

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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    Torisu, H., Kusuhara, K., Kira, R., Bassuny, W. M., Sakai, Y., Sanefuji, M., Takemoto, M., & Hara, T. (2004). Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis. Neurology, 62(3), 457-460. https://doi.org/10.1212/01.WNL.0000106940.95749.8E