Carr Edward J, Clatworthy Menna R, Lowe Christopher E, Todd John A, Wong Andrew, Vyse Timothy J, Kamesh Lavanya, Watts Richard A, Lyons Paul A, Smith Kenneth G C
Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
BMC Med Genet. 2009 Mar 5;10:22. doi: 10.1186/1471-2350-10-22.
Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA) - associated systemic vasculitis (AAV) with SNPs in the IL2RA region and to correlate genotype with serum levels of IL-2RA.
Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients), and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D) and rs2104286 with multiple sclerosis (MS) and T1D.
We show that SLE is associated with rs11594656 (P = 3.87 x 10-7) and there is some evidence of association of rs41295061 with AAV (P = 0.0122), which both have prior association with T1D. rs2104286, an MS and T1D - associated SNP in the IL2RA locus, is not associated with either SLE or AAV.
We have confirmed a previous suggestion that the IL2RA locus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within the IL2RA locus suggests that the IL2RA pathway may prove to play differing, as yet undefined, roles in each disease.
自身免疫性疾病很复杂，具有遗传和环境易感性因素。目的是检测系统性红斑狼疮（SLE）和抗中性粒细胞胞浆抗体（ANCA）相关系统性血管炎（AAV）与白细胞介素2受体α链（IL2RA）区域单核苷酸多态性（SNP）的遗传关联，并将基因型与IL - 2RA血清水平相关联。
我们使用了一个包含700多名AAV患者的队列、两项SLE病例对照研究和一个SLE三联体样本（总计超过1000名SLE患者），并采用TaqMan基因分型方法，检测了IL2RA基因座中的3个SNP，即rs11594656、rs2104286和rs41295061，每个SNP之前都与自身免疫性疾病有关联；rs11594656和rs41295061与1型糖尿病（T1D）有关，rs2104286与多发性硬化症（MS）和T1D有关。
我们发现SLE与rs11594656相关（P = 3.87×10 - 7），并且有一些证据表明rs41295061与AAV相关（P = 0.0122），这两个SNP之前都与T1D有关联。rs2104286是IL2RA基因座中一个与MS和T1D相关的SNP，与SLE或AAV均无关联。
我们证实了之前的一个观点，即IL2RA基因座与SLE相关，并显示出与AAV相关的一些证据。在AAV和SLE的静止期疾病中，可溶性IL - 2RA浓度与rs11594656基因型相关。自身免疫性疾病与IL2RA基因座内SNP的差异关联表明，IL2RA通路可能在每种疾病中发挥不同的、尚未明确的作用。
