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: 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
• Journal: Human genetics (Hum Genet) Vol. 127 Issue 4 Pg. 411-9 (Apr 2010) ISSN: 1432-1203 [Electronic] Germany
• PMID: 20066438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Apoptosis Regulatory Proteins
• DNA Primers
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Adolescent
• Alleles
• Antigens, CD (genetics)
• Apoptosis Regulatory Proteins (genetics)
• Asian People (genetics)
• Base Sequence
• Case-Control Studies
• Child
• Child, Preschool
• DNA Primers (genetics)
• Female
• Gene Expression
• Gene Frequency
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Japan
• Male
• Philippines
• Polymorphism, Single Nucleotide
• Programmed Cell Death 1 Receptor
• Promoter Regions, Genetic
• Subacute Sclerosing Panencephalitis (etiology, genetics)
• Young Adult