Yaghoobi Esmat, Abedian Saeed, Babani Omid, Izad Maryam
Dept. of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Dept. of Immunology, Mazandaran University Medical of Sciences, Sari, Iran.
Iran J Public Health. 2016 May;45(5):644-9.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by auto-reactive T cells against myelin antigens. T-cell immunoglobulin mucin -3 (TIM-3) is a negative regulator glycoprotein expressed by a range of immune cells, including, Th1 cells, activated CD8+ T cells and in a lower level on Th17 cells. A defect in TIM-3 regulation has been shown in multiple sclerosis patients. In humans, several single nucleotide polymorphisms (SNPs) have been identified in the TIM-3 gene and are associated with inflammatory diseases. The aim of this study was to analyze the association between TIM-3 -574A>C and -1516 C>A SNPs in the promoter region, and susceptibility to MS.
DNA samples from 102 patients and 102 healthy controls were genotyped using RFLP-PCR method.
In this case-control study, analysis of the alleles and genotypes revealed a significant higher frequency of C/C and lower frequency of A/C genotypes for -574 locus of TIM-3 gene in MS patients (P=0.0002). We also found that C/C genotype for locus of -1516 increased in MS patients, while A/C genotype decreased (P=0.012). Allele C of -574C/C and -1516 C>A SNPs were also more frequent in MS patients (P=0.036 and 0.0027 respectively).
-574 A>C and -1516 C>A SNPs in the promoter region of TIM3 gene may affect the disease susceptibility.
多发性硬化症（MS）是一种中枢神经系统（CNS）的自身免疫性疾病，由针对髓鞘抗原的自身反应性T细胞引起。T细胞免疫球蛋白粘蛋白-3（TIM-3）是一种由多种免疫细胞表达的负调节糖蛋白，包括Th1细胞、活化的CD8 + T细胞，在Th17细胞上表达水平较低。在多发性硬化症患者中已显示出TIM-3调节存在缺陷。在人类中，已在TIM-3基因中鉴定出几种单核苷酸多态性（SNP），并与炎症性疾病相关。本研究的目的是分析启动子区域中TIM-3 -574A>C和-1516 C>A SNP与MS易感性之间的关联。
使用RFLP-PCR方法对102例患者和102例健康对照的DNA样本进行基因分型。
在这项病例对照研究中，对等位基因和基因型的分析显示，MS患者中TIM-3基因-574位点的C/C基因型频率显著更高，A/C基因型频率更低（P = 0.0002）。我们还发现，-1516位点的C/C基因型在MS患者中增加，而A/C基因型减少（P = 0.012）。-574C/C和-1516 C>A SNP的等位基因C在MS患者中也更常见（分别为P = 0.036和0.0027）。
TIM3基因启动子区域的-574 A>C和-1516 C>A SNP可能影响疾病易感性。
