PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis
PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis
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DOI：
10.1007/s00439-009-0781-z
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发表时间：
2010-04-01
期刊：
影响因子：
5.3
通讯作者：
Hara, Toshiro
中科院分区：
文献类型：
--
作者：
Ishizaki, Yoshito;Yukaya, Naoko;Hara, Toshiro
虽然亚急性硬化性全脑炎（SSPE）的确切发病机制仍有待确定，但我们之前的数据表明，宿主对SSPE的易感性可能与遗传有关。在慢性病毒感染期间，病毒特异性细胞毒性T淋巴细胞表现出较差的效应功能。由于共抑制分子参与T淋巴细胞的抑制，我们研究了编码共抑制分子的基因的单核苷酸多态性（snp）是否与SSPE的易感性有关。在日本和菲律宾SSPE患者和对照中对8个基因（CTLA4、CD80、CD86、PD1、PDL1、PDL2、BTLA和HVEM）共20个snp进行了关联研究，并对PD1基因的4个snp进行了单倍型分析。然后，我们研究了两种单倍型启动子活性的功能差异，并比较了SSPE和对照之间PD1的表达水平。日本和菲律宾SSPE患者中含有-606G等位基因的PD1 GCG(C)单倍型的频率显著高于对照。-606G基因的启动子活性显著高于-606A基因的启动子活性。SSPE患者中PD1的表达水平明显高于对照组。我们的研究结果表明，PD1基因与SSPE的遗传易感性有关。
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.