Association of toll-like receptor 3 gene polymorphism with subacute sclerosing panencephalitis

Innate immunity plays an important role in measles virus (MV) infection. MV-derived double-stranded RNA is recognized by toll-like receptor 3 (TLR3), retinoic acid-inducible protein I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). We investigated whether genes encoding these molecules contributed to the development of subacute sclerosing panencephalitis (SSPE) in Japanese individuals. Four single nucleotide polymorphisms (SNPs) of the three genes (TLR3 rs3775291:Leu412Phe, RIG1 rs277729 and rs9695310, and MDA5 rs4664463) were assessed in 40 SSPE patients and 84 controls. Because the TLR3 SNP showed a positive association with SSPE, three additional SNPs were subjected to haplotype analysis. The frequency of 412Phe allele of TLR3 rs3775291 in SSPE patients was significantly higher than that in controls (P = .03). In haplotype analysis of four SNPs in the TLR3 gene, the frequency of -7C/IVS3 + 71C/Phe412/c.1377C haplotype was significantly increased in SSPE patients (P = .006, odds ration [OR]: 2.2). TLR3 gene may confer host genetic susceptibility to SSPE in Japanese individuals. Journal of NeuroVirology (2008) 14, 486-491.