Chromosome 17p12-q11 harbors susceptibility loci for systemic lupus erythematosus
Chromosome 17p12-q11 harbors susceptibility loci for systemic lupus erythematosus
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DOI：
10.1007/s00439-004-1145-3
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发表时间：
2004-08-01
期刊：
影响因子：
5.3
通讯作者：
Alarcón-Riquelme, ME
中科院分区：
文献类型：
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作者：
Johansson, CM;Zunec, R;Alarcón-Riquelme, ME
系统性红斑狼疮 (SLE) 是一种自身免疫性疾病，其特征是存在针对细胞内成分的自身抗体、免疫复合物的形成以及多个器官（通常是皮肤和肾小球）的炎症。该疾病的病因尚不清楚，但很可能是遗传和环境因素相互作用的结果。为了确定系统性红斑狼疮的易感位点，我们使用覆盖阿根廷、意大利和欧洲家庭整个基因组的微卫星标记进行了基因组扫描。结果揭示了一种异质性疾病，在不同的家庭中具有不同的易感位点。我们在阿根廷家族中发现了与染色体 17p12-q11 的显着连锁。当假设显性遗传模型时 (Z=3.88)，最大 LOD 分数由标记 D17S1294 与 D17S1293 组合给出。我们还分析了 NOS2A 基因启动子区域的重复，该区域是该区域的强候选基因，但没有发现关联。 17 号染色体上的基因座先前已在多发性硬化症家族的遗传研究中被确定。在 1p35、1q31、3q26、5p15、11q23 和 19q13 处发现了其他几个有趣的区域，证实了先前确定的 SLE 或其他自身免疫性疾病的位点。
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against intracellular components, the formation of immune complexes, and inflammation in various organs, typically the skin and kidney glomeruli. The etiology of the disease is not well understood but is most likely the result of the interaction between genetic and environmental factors. In order to identify susceptibility loci for SLE, we have performed genome scans with microsatellite markers covering the whole genome in families from Argentina, Italy, and Europe. The results reveal a heterogeneous disease with different susceptibility loci in different family sets. We have found significant linkage to chromosome 17p12-q11 in the Argentine set of families. The maximum LOD score was given by marker D17S1294 in combination with D17S1293, when assuming a dominant inheritance model (Z=3.88). We also analyzed a repeat in the promoter region of the NOS2A gene, a strong candidate gene in the region, but no association was found. The locus on chromosome 17 has previously been identified in genetic studies of multiple sclerosis families. Several other interesting regions were found at 1p35, 1q31, 3q26, 5p15, 11q23 and 19q13, confirming previously identified loci for SLE or other autoimmune diseases.