title: PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis.
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.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. ishizaki@pediatr.med.kyushu-u.ac.jp
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ishizaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Yukaya
authors.forename: Koichi
authors.initials: K
authors.lastname: Kusuhara
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kira
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Torisu
authors.forename: Kenji
authors.initials: K
authors.lastname: Ihara
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Sakai
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sanefuji
authors.forename: Judy R
authors.initials: JR
authors.lastname: Pipo-Deveza
authors.forename: Catherine Lynn T
authors.initials: CL
authors.lastname: Silao
authors.forename: Benilda C
authors.initials: BC
authors.lastname: Sanchez
authors.forename: Marissa B
authors.initials: MB
authors.lastname: Lukban
authors.forename: Aida M
authors.initials: AM
authors.lastname: Salonga
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D010679:Philippines; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D011401:Promoter Regions, Genetic; D013344:Subacute Sclerosing Panencephalitis / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor