Li Guanggang, Xu Ruxiang, Cao Yinghua, Xie Xiaodong, Zheng Zhendong
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Command, Beijing, 100700, China.
Inflammation. 2014 Dec;37(6):2030-9. doi: 10.1007/s10753-014-9935-9.
There has been more and more evidence to confirm the essential role of inflammatory processes in the development of ischemic stroke. Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the association between IL-21 polymorphisms and ischemic stroke, and the effects of these polymorphisms on gene expression. Two polymorphisms in IL-21, rs907715G/A and rs4833837A/G, were identified in 278 ischemic stroke patients and 282 healthy controls. Results showed that frequencies of rs907715GA and AA genotypes were significantly increased in cases than in controls (odd ratio (OR) = 1.49, 95% confidence interval (CI): 1.01-2.14, P = 0.042; OR = 2.21, 95% CI: 1.38-3.53, P = 0.001). Similarly, rs907715A allele revealed a positive association with the disease (OR = 1.52, P = 0.001). The rs4833837A/G polymorphism did not show any correlation with ischemic stroke. We further evaluated IL-21 messenger RNA (mRNA) and protein levels in peripheral blood mononuclear cells (PBMCs) from subjects carrying different polymorphism genotypes. Results revealed that subjects carrying polymorphic rs907715GA and AA genotypes had significantly higher IL-21 mRNA levels, whereas protein level was increased only in subjects with rs907715AA genotype. Serum level of IL-21 was also significantly elevated in subjects with rs907715AA genotype. These data suggest that IL-21 polymorphism is associated with increased susceptibility to ischemic stroke possibly by upregulating gene expression.
越来越多的证据证实炎症过程在缺血性脑卒中的发生发展中起重要作用。白细胞介素-21（IL-21）是最近发现的一种依赖CD132的细胞因子，在调节炎症中起关键作用。本研究的目的是了解IL-21基因多态性与缺血性脑卒中的关联，以及这些多态性对基因表达的影响。在278例缺血性脑卒中患者和282例健康对照中鉴定出IL-21基因的两个多态性位点，即rs907715G/A和rs4833837A/G。结果显示，rs907715GA和AA基因型在病例组中的频率显著高于对照组（比值比（OR）=1.49，95%置信区间（CI）：1.01-2.14，P=0.042；OR=2.21，95%CI：1.38-3.53，P=0.001）。同样，rs907715A等位基因与该疾病呈正相关（OR=1.52，P=0.001）。rs4833837A/G多态性与缺血性脑卒中无任何相关性。我们进一步评估了携带不同多态性基因型受试者外周血单个核细胞（PBMC）中IL-21信使核糖核酸（mRNA）和蛋白水平。结果显示，携带rs907715GA和AA多态性基因型的受试者IL-21 mRNA水平显著升高，而蛋白水平仅在rs907715AA基因型的受试者中升高。rs907715AA基因型受试者的血清IL-21水平也显著升高。这些数据表明，IL-21基因多态性可能通过上调基因表达而增加缺血性脑卒中的易感性。
