Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis.

Abstract:

BACKGROUND:The antivirally active MxA protein is induced by interferon (IFN) alpha/beta 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.

journal_name

Neurology

journal_title

Neurology

authors

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

doi

10.1212/01.wnl.0000106940.95749.8e

subject

Has Abstract

pub_date

2004-02-10 00:00:00

pages

457-60

issue

3

eissn

0028-3878

issn

1526-632X

journal_volume

62

pub_type

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