Aker Sendogan, Bantis Christos, Reis Philip, Kuhr Nicola, Schwandt Christina, Grabensee Bernd, Heering Peter, Ivens Katrin
Department of Nephrology, Heinrich-Heine University, Germany.
Nephrol Dial Transplant. 2009 Sep;24(9):2847-51. doi: 10.1093/ndt/gfp141. Epub 2009 Apr 6.
Inflammation is a well recognized central component of atherosclerotic processes in chronic kidney disease. Interleukin-6 (IL-6) levels are a strong determinant of cardiovascular mortality in dialysis patients. We evaluated the impact of IL-6 gene G-174C polymorphism associated with modified IL-6 production on the development of coronary artery disease (CAD), cardiovascular events and mortality in chronic dialysis patients.
We studied n = 463 patients on chronic dialysis with angiographically confirmed (n = 218) or excluded (n = 245) CAD followed up for 65 months after initiation of dialysis. Monitored were arterial hypertension, diabetes mellitus, hyperlipidemia, smoking, CRP and fibrinogen. IL-6 gene G-174C polymorphism was determined by PCR amplification.
The CC genotype was associated with an impaired patient survival (p < 0.05) remaining an independent risk factor for death in multivariate analysis (HR for CC genotype: 3.58, CI: 1.41-9.07, p < 0.01). CC genotype carrying CAD patients suffered significant frequently cardiovascular events (revascularization, myocardial infarction, death) compared to GG/GC genotype carriers (85.2% vs. 66.5, p < 0.05). However, the IL-6 gene G-174C polymorphism was not related to the onset and development of CAD itself (ns) and the inflammation parameters CRP and fibrinogen did not differ between the genotypes under investigation (ns).
Our results suggest that IL-6 gene G-174C polymorphism is associated with the incidence of cardiovascular events and mortality in chronic dialysis patients.
炎症是慢性肾脏病动脉粥样硬化进程中一个公认的核心组成部分。白细胞介素-6(IL-6)水平是透析患者心血管死亡率的一个重要决定因素。我们评估了与IL-6产生改变相关的IL-6基因G-174C多态性对慢性透析患者冠心病(CAD)发生、心血管事件及死亡率的影响。
我们研究了463例接受慢性透析的患者,其中经血管造影证实有CAD的患者218例,排除CAD的患者245例,在开始透析后随访65个月。监测指标包括动脉高血压、糖尿病、高脂血症、吸烟、CRP和纤维蛋白原。通过PCR扩增测定IL-6基因G-174C多态性。
CC基因型与患者生存率受损相关(p<0.05),在多变量分析中仍是死亡的独立危险因素(CC基因型的风险比:3.58,可信区间:1.41-9.07,p<0.01)。与GG/GC基因型携带者相比,携带CC基因型的CAD患者发生心血管事件(血运重建、心肌梗死、死亡)的频率显著更高(85.2%对66.5%,p<0.05)。然而,IL-6基因G-174C多态性与CAD本身的发生和发展无关(无统计学意义),且所研究基因型之间的炎症参数CRP和纤维蛋白原无差异(无统计学意义)。
我们的结果表明,IL-6基因G-174C多态性与慢性透析患者心血管事件的发生率及死亡率相关。