Abstract:
The inducible T-cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen-presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case-control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (-693 G/A) and rs10932029 (IVS1 + 173 T/C); using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss.20. Our results revealed a significant association between ICOS gene rs11889031 > CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p = .001, odds ratio [OR] = 2.18 IC [1.36-3.49]); codominant genetic model 2, (C/C vs. T/T) p = .007, OR = 15.29 IC [1.97-118.5]); dominant genetic model, (C/C vs. C/T + T/T) p = .0001, OR = 2.44 IC [1.53-3.9]). Besides, there was a marginal association between rs11889031 > TT genotype and T allele with a protective role from SLE (recessive genetic model, p = .016, OR = 0.08 IC [0.01-0.63] and p = 7.6904E - 05, OR = 0.43 IC = [0.28-0.66], respectively). Moreover, statistical analysis indicated that the rs11889031 > CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti-SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031 > CC genotype with SLE, in contrast to a protective effect of rs11889031 > TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker.
摘要:
诱导型T细胞共刺激因子(ICOS)可能通过调节T细胞与抗原呈递细胞之间的相互作用在适应性免疫中起重要作用。这种分子的破坏会导致自身免疫性疾病,特别是系统性红斑狼疮(SLE)。在这项研究中,我们旨在探讨ICOS基因多态性与SLE之间的可能关联及其对疾病易感性和临床结局的影响.另一个目的是评估这些多态性对RNA表达的潜在影响。病例对照研究,包括151例SLE患者,和291个性别匹配的无关健康对照(HC),和地理起源,对ICOS基因中的两个多态性进行了基因型:rs11889031(-693G/A)和rs10932029(IVS1173T/C);使用聚合酶链反应(PCR)-限制性片段长度多态性方法。通过直接测序验证不同的基因型。通过定量PCR评估SLE患者外周血单个核细胞和HC中ICOSmRNA的表达水平。使用Shesis和spss.20分析结果。我们的结果表明ICOS基因rs11889031>CC基因型与SLE疾病之间存在显着关联(共显性遗传模型1,(C/Cvs.C/T),p=.001,比值比[OR]=2.18IC[1.36-3.49]);共显性遗传模型2,(C/Cvs.T/T)p=.007,OR=15.29IC[1.97-118.5]);显性遗传模型,(C/Cvs.C/T+T/T)p=.0001,OR=2.44IC[1.53-3.9])。此外,rs11889031>TT基因型和T等位基因之间存在边缘关联,具有对SLE的保护作用(隐性遗传模型,p=.016,OR=0.08IC[0.01-0.63],p=7.6904E-05,OR=0.43IC=[0.28-0.66],分别)。此外,统计学分析表明rs11889031>CC基因型与SLE的临床和血清学表现有关,包括血压,和SLE患者抗SSA抗体的产生。然而,ICOS基因rs10932029多态性与SLE易感性无关。在另一边,我们没有注意到两种选择的多态性对ICOSmRNA基因表达水平有任何影响.研究表明ICOSrs11889031>CC基因型与SLE有显著的易感关联,与rs11889031>TT基因型在突尼斯患者中的保护作用相反。我们的结果表明,ICOSrs11889031可能是SLE的危险因素,并且可以用作遗传易感性生物标志物。