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Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis

From the Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Address correspondence and reprint requests to Dr. H. Torisu, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 20812-8582, Japan; e-mail: htorys{at}pediatr.med.kyushu-u.ac.jp

Background: The antivirally active MxA protein is induced by interferon (IFN) /ß 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.

Received July 11, 2003. Accepted in final form October 15, 2003.