Contrasting genetic association of IL2RA with SLE and ANCA-associated vasculitis.
Contrasting genetic association of IL2RA with SLE and ANCA-associated vasculitis.
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DOI：
10.1186/1471-2350-10-22
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发表时间：
2009-03-05
影响因子：
--
通讯作者：
Smith KG
中科院分区：
文献类型：
--
作者：
Carr EJ;Clatworthy MR;Lowe CE;Todd JA;Wong A;Vyse TJ;Kamesh L;Watts RA;Lyons PA;Smith KG
自身免疫性疾病是复杂的，有遗传和环境易感因素。本研究旨在探讨系统性红斑狼疮(SLE)和抗中性粒细胞胞浆抗体(ANCA)相关性系统性小血管炎(AAV)与IL2RA区SNPs的遗传关联性，以及IL-2RA水平与基因分型的相关性。使用700多名AAV患者的队列、两项SLE病例对照研究和一组SLE三人组(总计1000多名SLE患者)和TaqMan基因分型方法，我们检测了IL2RA基因座的3个SNPs，rs11594656、rs2104286和rs41295061，每个都与自身免疫性疾病有关；rs11594656和rs41295061与1型糖尿病(T1D)和rs2104286合并多发性硬化症(MS)和T1D。我们发现系统性红斑狼疮与rs11594656(P=3.87×10-7)相关，rs41295061与AAV有关联(P=0.0122)，两者都与T1D有关联。Rs2104286是一个位于IL2RA基因座的MS和T1D相关SNP，与SLE和AAV均无关联。我们已经证实了先前提出的IL2RA基因与SLE相关的说法，并显示了一些与AAV相关的证据。在AAV和SLE的静止期疾病中，sIL-2RA浓度与rs11594656基因相关。自身免疫性疾病与IL2RA基因内SNPs的不同关联表明，IL2RA途径可能在每种疾病中发挥不同的作用，但尚未确定。
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 × 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.
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影响因子：
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作者：
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Modica, M A