Human Genetics

, Volume 127, Issue 4, pp 411–419

PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis

Authors

    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
  • Naoko Yukaya
    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
  • Koichi Kusuhara
    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
    • Department of PediatricsUniversity of Occupational and Environmental Health School of Medicine
  • Ryutaro Kira
    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
  • Hiroyuki Torisu
    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
  • Kenji Ihara
    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
  • Yasunari Sakai
    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
  • Masafumi Sanefuji
    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
  • Judy R. Pipo-Deveza
    • Department of Pediatrics and Neurosciences, Philippine General HospitalUniversity of the Philippines
  • Catherine Lynn T. Silao
    • Department of Pediatrics and Neurosciences, Philippine General HospitalUniversity of the Philippines
    • Institute of Human GeneticsNational Institutes of Health
  • Benilda C. Sanchez
    • Department of Pediatrics and Neurosciences, Philippine General HospitalUniversity of the Philippines
  • Marissa B. Lukban
    • Department of Pediatrics and Neurosciences, Philippine General HospitalUniversity of the Philippines
  • Aida M. Salonga
    • Department of Pediatrics and Neurosciences, Philippine General HospitalUniversity of the Philippines
  • Toshiro Hara
    • Department of Pediatrics, Graduate School of Medical SciencesKyushu University
Original Investigation

DOI: 10.1007/s00439-009-0781-z

Cite this article as:
Ishizaki, Y., Yukaya, N., Kusuhara, K. et al. Hum Genet (2010) 127: 411. doi:10.1007/s00439-009-0781-z

Abstract

Although the exact pathogenesis of subacute sclerosing panencephalitis (SSPE) remains to be determined, our previous data suggested a genetic contribution to the host susceptibility to SSPE. During chronic viral infection, virus-specific cytotoxic T lymphocytes display poor effector functions. Since co-inhibitory molecules are involved in the suppression of T lymphocytes, we investigated whether single nucleotide polymorphisms (SNPs) of genes encoding co-inhibitory molecules contributed to a susceptibility to SSPE. Association studies on a total of 20 SNPs in 8 genes (CTLA4, CD80, CD86, PD1, PDL1, PDL2, BTLA and HVEM) and subsequent haplotype analysis of 4 SNPs in the PD1 genes were performed in Japanese and Filipino SSPE patients and controls. Then, we investigated a functional difference in promoter activity of two haplotypes and compared the expression levels of PD1 between SSPE and controls. The frequency of GCG(C) haplotype of PD1 containing −606G allele was significantly higher in SSPE patients than in controls both in Japanese and in Filipinos. The promoter activity was significantly higher in the construct with −606G allele than in that with −606A allele. The expression levels of PD1 were significantly higher in SSPE patients than in the controls. Our results suggested that the PD1 gene contributed to a genetic susceptibility to SSPE.

Copyright information

© Springer-Verlag 2010