Deser Serkan Burc, Bayoglu Burcu, Besirli Kazım, Cengiz Mujgan, Arapi Berk, Junusbekov Yerik, Dirican Ahmet, Arslan Caner
Department of Cardiovascular Surgery, Medical Faculty, 19 Mayis University, Samsun, 55139, Turkey.
Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Heart Vessels. 2016 Jun;31(6):976-84. doi: 10.1007/s00380-015-0753-2. Epub 2015 Oct 5.
Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.
外周动脉疾病（PAD）通常是指由下肢动脉粥样硬化性狭窄引起的下肢血管缺血。白细胞介素18（IL18）是一种多效性促炎细胞因子，据报道在心血管疾病中作为一种炎症生物标志物发挥作用。IL18的活性由高亲和力的天然存在的IL18结合蛋白（IL18BP）平衡。本研究旨在确定IL18、IL18BP mRNA水平以及先前与IL18基因转录活性相关的-137 G/C（rs187238）多态性是否与PAD的病因有关。分别通过定量实时聚合酶链反应（qRT-PCR）和逆转录聚合酶链反应（RT-PCR）测定了55例PAD患者（26例主-髂动脉型，29例股-腘动脉型）和61例无疾病对照者外周血单核细胞中的IL18、IL18BP mRNA水平以及-137 G/C（rs187238）多态性。与健康对照相比，PAD患者的IL18 mRNA水平升高（p = 0.09）；然而，未达到统计学显著水平，在主-髂动脉型和股-腘动脉型闭塞性PAD亚组之间也无显著差异（p = 0.285）。然而，与对照组相比，PAD组的IL18BP mRNA水平显著降低（p < 0.001）。rs187238多态性的基因型频率在PAD患者和对照之间无显著差异（p = 0.385）。在PAD患者中，IL18 mRNA水平分别与甘油三酯和低密度脂蛋白胆固醇水平显著相关（p = 0.003，p = 0.014）。在对照中，高密度脂蛋白胆固醇水平与IL18 mRNA水平呈负相关（p = 0.05）。本报告是一项初步研究，显示了IL18、IL18BP mRNA水平与PAD之间的关联，并表明IL18基因可能与PAD患者的甘油三酯和低密度脂蛋白胆固醇水平存在显著关系。
