Abstract
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.
Acknowledgements
The authors thank Drs. H. Hattori (Osaka City University Medical School), S. Yamashita (Kanagawa Children's Medical Center), K. Nihei (National Children's Hospital), N. Koide (National Iwaki Hospital), H. Aiba (Shizuoka Children's Hospital), T. Okada (Kochi Medical School), F. Hamada (Hosogi Hospital), N. Koyama (Toyohashi Municipal Hospital), Y. Hirata (Hamamatsu Medical Center), C. Baba (Red Cross Nagasaki Atomic Bomb Hospital), A.Ono (Saiseikai Izumio Hospital), A. Tomoda (Kumamoto University), M. Funahashi (Tokyo Children's Rehabilitation Hospital), T. Kurokawa (National Nishi–Beppu Hospital), R. Sakuta (Dokkyo University Koshigaya Hospital), M. Miyazaki (Tokushima University), K. Shioya (National Nichinan Hospital), N. Nagano (Asahikawa City Hospital), T. Ishizu (National Saishunso Hospital), K. Gondo and Y. Tokunaga (Kyushu University), and K. Watanabe (Kagoshima Municipal Hospital) for providing patient samples. This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (No. 16390304), Health and Labour Sciences Research Grant for Research on Measures for Intractable Diseases (Prion Disease and Slow Virus Infections) from the Ministry of Health, Labour and Welfare of Japan.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.