Kikuchi Seiji, Miyagishi Ryuji, Fukazawa Toshiyuki, Yabe Ichiro, Miyazaki Yusei, Sasaki Hidenao
Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
J Neuroimmunol. 2005 Oct;167(1-2):170-4. doi: 10.1016/j.jneuroim.2005.06.021.
TNF-related apoptosis inducing ligand (TRAIL) has been reported to induce apoptosis of autoreactive T cells and other inflammatory cells, and thus, it is a strong candidate gene for involvement in the development of autoimmune diseases. We investigated single nucleotide polymorphisms (SNPs) in the coding region of the gene at position 1595 in exon 5 in 128 Japanese patients with conventional/classical multiple sclerosis (MS) and 158 healthy controls. Patients with optico-spinal MS (OSMS) or atypical clinical attacks were excluded from the study. The frequency of CC genotype at position 1595 was significantly different between patients and controls (p=0.0027), and the C allele was more prevalent in the patients than in the controls (p=0.0138, OR=1.546, 95% CI=1.092-2.188). Logistic analysis, adjusted for HLA-DRB1*1501-positivity, revealed the independent association of the CC genotype with susceptibility to MS (p=0.0006, OR=2.393, 95% CI=1.453-3.943). There were no significant associations between +1595 polymorphism and the clinical features of MS. The results indicate that the presence of the CC genotype at position 1595 in exon 5 represents a higher risk of MS.
据报道,肿瘤坏死因子相关凋亡诱导配体(TRAIL)可诱导自身反应性T细胞和其他炎性细胞凋亡,因此,它是参与自身免疫性疾病发生发展的一个强有力的候选基因。我们调查了128例日本传统/经典型多发性硬化症(MS)患者和158名健康对照者第5外显子1595位基因编码区的单核苷酸多态性(SNP)。视神经脊髓型MS(OSMS)患者或具有非典型临床发作的患者被排除在研究之外。患者和对照者之间1595位CC基因型的频率存在显著差异(p=0.0027),并且C等位基因在患者中比在对照者中更普遍(p=0.0138,OR=1.546,95%CI=1.092-2.188)。经HLA-DRB1*1501阳性校正的逻辑分析显示CC基因型与MS易感性独立相关(p=0.0006,OR=2.393,95%CI=1.453-3.943)。+1595多态性与MS的临床特征之间无显著关联。结果表明,第5外显子1595位CC基因型的存在代表MS的较高风险。