Wang Peng, He Qian, Liu Chen, He Shi Zhen, Zhu Shou Yan, Li Ying Wen, Su Wei, Xiang Shu Tian, Zhao Bo
Department of Radiology, the Second People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Medicine (Baltimore). 2017 Nov;96(46):e8522. doi: 10.1097/MD.0000000000008522.
Accumulating evidence indicates interleukin-1 (IL-1) is a critical mediator of inflammatory responses in ischemic stroke (IS). The aim of this study was to investigate whether rs3783553 in the 3'-untranslated region of IL-1A was associated with the risk of IS. In this hospital-based case-control study, we genotyped the rs3783553 using polymerase chain reaction in 316 patients with IS and 332 age, sex, and ethnicity-matched controls. Plasma level of IL-1α was measured by enzyme-linked immunosorbent assay. The relative luciferase activities were measured by the Dual Luciferase assay system. The presence of ins/ins genotype was associated with higher odds ratios (ORs) of IS compared with del/del genotype (ins/ins vs del/del: adjusted OR 1.77, 95% confidence interval [CI] 1.06-2.98; recessive model: adjusted OR 1.69, 95% CI 1.06-2.70). The higher risk of IS was also observed in allele comparison (adjusted OR 1.29, 95% CI 1.00-1.65). Multivariate logistic regression analysis showed that age, hypertension, total cholesterol, triglyceride, low-density lipoprotein, and rs3783553ins/ins genotypes were independent risk factors for IS. Plasma level of IL-1α was higher among IS patients compared with controls (P = .03). Notably, IS patients with the TTCA/TTCA genotype had a higher level of IL-1α compared with those with the del/del genotype (P = .01). Luciferase reporter assay showed that the vector containing the TTCA del allele exhibited a reduced transcriptional activity in the presence of miR-122 and miR-378. These findings indicate that IL-1A rs3783553 ins/ins genotype may increase the susceptibility to IS, possibly by interrupting the binding site of miR-122 and miR-378.
越来越多的证据表明，白细胞介素-1（IL-1）是缺血性中风（IS）炎症反应的关键介质。本研究的目的是调查IL-1A 3'-非翻译区的rs3783553是否与IS风险相关。在这项基于医院的病例对照研究中，我们使用聚合酶链反应对316例IS患者和332例年龄、性别和种族匹配的对照进行了rs3783553基因分型。通过酶联免疫吸附测定法测量血浆IL-1α水平。使用双荧光素酶测定系统测量相对荧光素酶活性。与del/del基因型相比，ins/ins基因型的存在与IS的较高比值比（OR）相关（ins/ins与del/del：调整后的OR 1.77，95%置信区间[CI] 1.06-2.98；隐性模型：调整后的OR 1.69，95%CI 1.06-2.70）。在等位基因比较中也观察到IS的较高风险（调整后的OR 1.29，95%CI 1.00-1.65）。多变量逻辑回归分析表明，年龄、高血压、总胆固醇、甘油三酯、低密度脂蛋白和rs3783553 ins/ins基因型是IS的独立危险因素。与对照组相比，IS患者的血浆IL-1α水平更高（P = 0.03）。值得注意的是，与del/del基因型患者相比，TTCA/TTCA基因型的IS患者IL-1α水平更高（P = 0.01）。荧光素酶报告基因测定表明，含有TTCA del等位基因的载体在miR-122和miR-378存在下表现出降低的转录活性。这些发现表明，IL-1A rs3783553 ins/ins基因型可能通过中断miR-122和miR-378的结合位点来增加对IS的易感性。
