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日本多发性硬化症患者中肿瘤坏死因子相关凋亡诱导配体(TRAIL)基因多态性

TNF-related apoptosis inducing ligand (TRAIL) gene polymorphism in Japanese patients with multiple sclerosis.

作者信息

Kikuchi Seiji, Miyagishi Ryuji, Fukazawa Toshiyuki, Yabe Ichiro, Miyazaki Yusei, Sasaki Hidenao

机构信息

Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638, Japan.

出版信息

J Neuroimmunol. 2005 Oct;167(1-2):170-4. doi: 10.1016/j.jneuroim.2005.06.021.

Abstract

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.

摘要

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。

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