Contribution of the interleukin 4 gene to susceptibility to subacute sclerosing panencephalitis.

BACKGROUND Although the exact pathogenesis of subacute sclerosing panencephalitis (SSPE) remains to be determined, both viral and host factors seem to be involved. OBJECTIVE To identify host genetic factors involved in the development of SSPE. METHODS We investigated the association of polymorphisms in the T helper (Th)1 and Th2 cytokine, and related genes (interferon [IFN]-gamma, IFN-gamma receptor 1 [IFN-gamma R1], IFN-gammaR2 [IRF-1], interleukin 12 receptor beta 1 [IL-12Rbeta1], IL-4, IL-4R, and IL-10 genes) with SSPE in Japanese subjects. RESULTS A significant association (P =.03) was observed between SSPE and the T allele of the biallelic polymorphism at position -589 in the promoter region of the IL-4 gene. The IRF-1 allele 1 tended to interact with the IL-4 promoter -589 T genotype in the development of SSPE (P =.06), as judged on logistic regression analysis. The frequency of the genotype combination of IL-4 promoter -589 T and IRF-1 allele 1 (at least 1 allele) in patients with SSPE was much higher than that in the controls (47.7% vs 22.0%; P =.003, chi2 analysis). However, there was no association between other polymorphisms and SSPE. CONCLUSION To our knowledge, this study is the first to demonstrate the possibility that the IL-4 promoter gene -589 T gene polymorphism with increased IL-4 synthesis in combination with IRF-1 allele 1 confers host genetic susceptibility to SSPE in Japanese subjects.