PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis
| Autor: | Catherine Lynn T. Silao, Ryutaro Kira, Masafumi Sanefuji, Koichi Kusuhara, Yoshito Ishizaki, Marissa B. Lukban, Toshiro Hara, Yasunari Sakai, Judy R. Pipo-Deveza, Benilda C. Sanchez, Aida M. Salonga, Kenji Ihara, Hiroyuki Torisu, Naoko Yukaya |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Candidate gene Adolescent Philippines Programmed Cell Death 1 Receptor BTLA Gene Expression Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Subacute sclerosing panencephalitis Young Adult Asian People Gene Frequency Japan Antigens CD Genetics Genetic predisposition medicine Humans Genetic Predisposition to Disease Allele Child Promoter Regions Genetic Allele frequency Genetics (clinical) Alleles DNA Primers Base Sequence fungi Haplotype virus diseases medicine.disease nervous system diseases Haplotypes Case-Control Studies Child Preschool Immunology Female Subacute Sclerosing Panencephalitis Apoptosis Regulatory Proteins |
| Zdroj: | Human genetics. 127(4) |
| ISSN: | 1432-1203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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