02470daf-ffbd-4ad9-84af-64051fb1261a
title
Functional  MxA  promoter polymorphism associated with subacute sclerosing panencephalitis.
9065d996-bfad-420f-a762-9d86a1f34a27
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.