Haimila Katri E, Partanen Jukka A, Holopainen Päivi M
Finnish Red Cross Blood Transfusion Service, Department of Tissue Typing, Kivihaantie 7, 00310 Helsinki, Finland.
Immunogenetics. 2002 Mar;53(12):1028-32. doi: 10.1007/s00251-002-0431-2. Epub 2002 Feb 6.
Inducible costimulator (ICOS) is a novel receptor belonging to the same family as CD28 and CTLA4, which regulate T-lymphocyte activation in the immune response. The genes for these molecules are located adjacent to each other on Chromosome 2q33. Many autoimmune diseases have been found to be genetically linked to or associated with genetic markers near the CTLA4 gene. However, as all three genes are closely linked and have related functions, it is possible that the findings could be explained by variation in CD28 or ICOS. Few data on genetic variation in the ICOS gene are available. We sequenced the ICOS gene in 13 healthy unrelated individuals and found eight single nucleotide polymorphisms. One was located in the first intron, and the others in the untranslated region of the last exon. The allele frequencies and linkage disequilibrium were determined from a population sample of 63 Finnish individuals. The results show that the ICOS gene is polymorphic, but no variation in the coding sequence was detected, implying that the genetic linkage of this gene region to autoimmune diseases may not result from structural variation in the ICOS molecule. These polymorphisms, however, should be useful in genetic studies of this candidate gene.
诱导性共刺激分子（ICOS）是一种与CD28和CTLA4同属一个家族的新型受体，它们在免疫反应中调节T淋巴细胞的激活。这些分子的基因在2号染色体q33区域彼此相邻。许多自身免疫性疾病已被发现与CTLA4基因附近的遗传标记存在遗传联系或关联。然而，由于这三个基因紧密连锁且功能相关，这些发现有可能是由CD28或ICOS的变异所解释。关于ICOS基因遗传变异的数据很少。我们对13名健康无亲缘关系的个体的ICOS基因进行了测序，发现了8个单核苷酸多态性。一个位于第一个内含子中，其他位于最后一个外显子的非翻译区。从63名芬兰个体的群体样本中确定了等位基因频率和连锁不平衡。结果表明，ICOS基因具有多态性，但未检测到编码序列的变异，这意味着该基因区域与自身免疫性疾病的遗传联系可能不是由ICOS分子的结构变异导致的。然而，这些多态性在该候选基因的遗传研究中应该是有用的。
