Human Genetics

, Volume 127, Issue 4, pp 411–419

PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis

  • Yoshito Ishizaki
  • Naoko Yukaya
  • Koichi Kusuhara
  • Ryutaro Kira
  • Hiroyuki Torisu
  • Kenji Ihara
  • Yasunari Sakai
  • Masafumi Sanefuji
  • Judy R. Pipo-Deveza
  • Catherine Lynn T. Silao
  • Benilda C. Sanchez
  • Marissa B. Lukban
  • Aida M. Salonga
  • Toshiro Hara
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

Authors and Affiliations

  • Yoshito Ishizaki
    • 1
  • Naoko Yukaya
    • 1
  • Koichi Kusuhara
    • 1
    • 4
  • Ryutaro Kira
    • 1
  • Hiroyuki Torisu
    • 1
  • Kenji Ihara
    • 1
  • Yasunari Sakai
    • 1
  • Masafumi Sanefuji
    • 1
  • Judy R. Pipo-Deveza
    • 2
  • Catherine Lynn T. Silao
    • 2
    • 3
  • Benilda C. Sanchez
    • 2
  • Marissa B. Lukban
    • 2
  • Aida M. Salonga
    • 2
  • Toshiro Hara
    • 1
  1. 1.Department of Pediatrics, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Pediatrics and Neurosciences, Philippine General HospitalUniversity of the PhilippinesManilaPhilippines
  3. 3.Institute of Human GeneticsNational Institutes of HealthManilaPhilippines
  4. 4.Department of PediatricsUniversity of Occupational and Environmental Health School of MedicineKitakyushuJapan