Ruiz-Larrañaga Otsanda, Migliorini Paola, Uribarri Maria, Czirják László, Alcaro Maria C, Del Amo Jokin, Iriondo Mikel, Manzano Carmen, Escorza-Treviño Sergio, Estonba Andone
Genetics, Physical Anthropology and Animal Physiology Department, University of the Basque Country (UPV/EHU), Leioa, Spain.
Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Clin Rheumatol. 2016 May;35(5):1161-8. doi: 10.1007/s10067-016-3235-8. Epub 2016 Mar 28.
Epidemiological studies suggest a strong contribution of genetic factors in the pathogenesis of systemic lupus erythematosus (SLE). In the last decades, many risk loci have been identified in several genetic association studies following both candidate gene and genome-wide approaches. The present work was conducted by GAPAID (Genes And Proteins for AutoImmunity Diagnostics) consortium with a dual aim: to replicate the association of several previously reported SLE susceptibility loci in an independent European sample and to explore their relation with some disease subphenotypes. A total of 48 single nucleotide polymorphisms (SNP) from 40 associated loci were typed in a cohort of 208 SLE patients and 152 controls from Rheumatology Units of the University Hospital of Pisa (Italy) and University of Pécs Medical Center (Hungary). Regression analyses were performed to detect disease susceptibility loci and to identify genes affecting specific disease manifestations (renal, neurological, or skin involvement; arthritis; secondary Sjögren syndrome; and secondary antiphospholipid syndrome). Association of previously described risk alleles from HLA locus has been replicated, while IRF5, BLK, ITGAM, and IRF8 loci have been found to be consistent with previous published results. In addition, two new subphenotype-specific associations have been detected: SNP rs5754217 (UBE2L3) with skin involvement and rs3093030 (ICAM1-ICAM4-ICAM5) with hematological disorders. Overall, results from GAPAID project are consistent with previously established associations for HLA, IRF5, BLK, ITGAM, and IRF8 SLE susceptibility loci and report for the first time two subphenotype-specific associations.
流行病学研究表明，遗传因素在系统性红斑狼疮（SLE）的发病机制中起着重要作用。在过去几十年中，通过候选基因和全基因组方法开展的多项基因关联研究已鉴定出许多风险基因座。本研究由GAPAID（自身免疫诊断的基因与蛋白质）联盟开展，具有双重目的：在一个独立的欧洲样本中复制先前报道的几个SLE易感基因座的关联，并探索它们与某些疾病亚表型的关系。在来自意大利比萨大学医院和匈牙利佩奇医科大学风湿病科的208例SLE患者和152例对照组成的队列中，对来自40个相关基因座的48个单核苷酸多态性（SNP）进行了分型。进行回归分析以检测疾病易感基因座，并识别影响特定疾病表现（肾脏、神经或皮肤受累；关节炎；继发性干燥综合征；以及继发性抗磷脂综合征）的基因。先前描述的HLA基因座风险等位基因的关联已得到复制，而IRF5、BLK、ITGAM和IRF8基因座的结果与先前发表的结果一致。此外，还检测到两个新的亚表型特异性关联：SNP rs5754217（UBE2L3）与皮肤受累相关，rs3093030（ICAM1-ICAM4-ICAM5）与血液系统疾病相关。总体而言，GAPAID项目的结果与先前确定的HLA、IRF5、BLK、ITGAM和IRF8 SLE易感基因座的关联一致，并首次报告了两个亚表型特异性关联。
