Douroudis Konstantinos, Laine Antti-Pekka, Heinonen Mirkka, Hermann Robert, Lipponen Kati, Veijola Riitta, Simell Olli, Knip Mikael, Uibo Raivo, Ilonen Jorma, Kisand Kalle
Immunology Group, IGMP, University of Tartu, Tartu, Estonia.
Hum Immunol. 2009 Jul;70(7):536-9. doi: 10.1016/j.humimm.2009.04.023. Epub 2009 Apr 17.
Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and inducible T-cell co-stimulator (ICOS) genes are important mediators of T-cell activation in autoimmune diseases. The aim of the current study was to assess the impact of CTLA-4 and ICOS genes on the susceptibility to type 1 diabetes among two populations with different disease incidence rates. Three single nucleotide polymorphisms (SNPs) within the CTLA-4 region (+49A/G, CT60A/G, CTBC217_1C/T) and two SNPs within the ICOS region (CTIC154_1 C/T, CTIC159 C/G) were genotyped in 955 control subjects and 574 diabetic patients of Estonian and Finnish descent. The current study confirms the involvement of the CTLA-4 but not the ICOS gene in susceptibility to type 1 diabetes. However, the risk alleles and the defined main risk haplotype were more common in the Finnish controls compared with the Estonians, indicating that this gene locus might also be one of the contributing factors to the higher disease incidence in Finland.
细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和诱导性T细胞共刺激分子（ICOS）基因是自身免疫性疾病中T细胞活化的重要介质。本研究的目的是评估CTLA-4和ICOS基因对两个疾病发病率不同的人群中1型糖尿病易感性的影响。在955名对照受试者以及574名爱沙尼亚和芬兰裔糖尿病患者中，对CTLA-4区域内的三个单核苷酸多态性（SNP）（+49A/G、CT60A/G、CTBC217_1C/T）以及ICOS区域内的两个SNP（CTIC154_1 C/T、CTIC159 C/G）进行了基因分型。本研究证实CTLA-4基因而非ICOS基因与1型糖尿病易感性有关。然而，与爱沙尼亚人相比，风险等位基因和确定的主要风险单倍型在芬兰对照人群中更为常见，这表明该基因位点可能也是芬兰疾病发病率较高的一个促成因素。
