Contribution of the Interleukin 4 Gene to Susceptibility to Subacute Sclerosing Panencephalitis

• Published in: Archives of neurology (Chicago) Vol. 59; no. 5; pp. 822 - 827
• Main Authors: Inoue, Takehiko, Kira, Ryutaro, Nakao, Futoshi, Ihara, Kenji, Bassuny, Wafaa M, Kusuhara, Koichi, Nihei, Kenji, Takeshita, Kenzo, Hara, Toshiro
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.05.2002
• Subjects: Adolescent; Biological and medical sciences; Child; Child, Preschool; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Human viral diseases; Humans; Infectious diseases; Interleukin-4 - genetics; Male; Medical sciences; Polymorphism, Single Nucleotide; Promoter Regions, Genetic - genetics; Subacute Sclerosing Panencephalitis - genetics; Viral diseases; Viral diseases of the nervous system; Human; Nervous system diseases; Cytokine; Th1 lymphocyte; Interleukin 12; Genetic determinism; Cerebral disorder; Inflammatory disease; Infection; Promoter; Allele; Interleukin 4; Gene; Sclerosing panencephalitis; Viral disease; Central nervous system disease; Risk factor; Th2 lymphocyte; Gamma interferon; Polymorphism; Subacute
• ISSN: 0003-9942; 2168-6149; 1538-3687; 2168-6157
• DOI: 10.1001/archneur.59.5.822

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]-γ, IFN-γ receptor 1 [IFN-γ R1], IFN-γR2 [IRF-1], interleukin 12 receptor β 1 [IL-12Rβ1], 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 Tgenotype 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, χ2 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.Arch Neurol. 2002;59:822-827-->