Abstract for presentation at 11th International Congress of Human Genetics

Genetic analysis of molecules related to dsRNA recognition in subacute sclerosing panencephalitis

  • Dr Megumi Takemoto, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Japan
  • Dr Koichi Kusuhara, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Japan
  • Dr Ryutaro Kira, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Japan
  • Dr Hiroyuki Torisu, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Japan
  • Dr Yoshito Ishizaki, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Japan
  • Dr Yasunari Sakai, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Japan
  • Dr Toshiro Hara, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Japan

    • The pathogenesis of subacute sclerosing panencephalitis (SSPE) is not fully clarified. Recognition of double strand RNA (dsRNA) by immune system is one of the key steps in innate immunity to viruses including measles virus (MV). In this study, we investigated the association of SNPs within the genes encoding molecules related to dsRNA recognition (TLR3, RIG-I, MDA5 and LGP2) with SSPE to further identify host genetic factors involved in the development of SSPE. We selected 7 SNPs with minor allele frequencies over 10% for analysis according to the information in the database of International HapMap Project (http://www.hapmap.org). Forty SSPE patients and 87 unrelated normal controls were genotyped using TaqMan SNP Genotyping Assay. Association studies were conducted by Chi-square analysis with a 2 x 2 contingency table. When a SNP showed significant association with SSPE, we also analyzed adjacent SNPs. The Ethics Committee of Kyushu University, Japan approved this study. As to TLR3, the frequency of T allele of the c.1234 C/T (L412F) polymorphism was significantly higher in SSPE patients (P= 0.028) than in controls. Although other SNPs showed no significant differences in allele frequency between SSPE patients and controls, haplotype analysis on c.1234 C/T and c.1377 C/T in perfect linkage disequilibrium (D'=1) demonstrated that frequency of TT haplotype was significantly higher in SSPE patients than in controls (P= 0.028). SNPs of RIGI, MDA5, and LGP2 tested did not show any association with SSPE. In the L412F polymorphism of TLR3, one of the leucine residues which constitute leucine-rich repeat, a characteristic structure of the ligand-binding domain, is replaced by phenylalanine. This substitution may cause a functional change of TLR3 in terms of its binding to dsRNA or TLR-related protein(s) and play a role in genetic susceptibility to SSPE through modulation of innate immunity to MV.

    Conference Organiser - ICMS Pty Ltd