Bittar Mohamad N, Carey John A, Barnard James, Fildes James E, Pravica Vera, Yonan Nizar, Hutchinson Ian V
Department of Cardiothoracic Surgery, South Manchester University Hospitals NHS Trust, Manchester, UK.
Heart Surg Forum. 2005;8(3):E140-5; discussion E145. doi: 10.1532/HSF98.20041120.
Levels of the proinflammatory cytokine interleukin 6 (IL-6) increase after surgery. The functional polymorphism in the IL-6 promoter region, G-174C, is associated with an increased risk of coronary heart disease. We investigated the genetic predisposition in IL-6 response to coronary revascularization and studied the association between the G-174C polymorphism, IL-6 levels, and clinical outcomes of surgery.
DNA was obtained from 96 consecutive patients who underwent elective coronary revascularization. Patients were genotyped for the IL-6 G-174C polymorphism by means of sequence-specific primer-polymerase chain reaction analysis. IL-6 levels were measured with an enzyme-linked immunosorbent assay on serum samples taken 3 hours postoperatively. IL-6 levels and genotypes (CC, CG, and GG) were correlated with perioperative clinical data.
The prevalences of the CC, CG, and GG IL-6 -174 genotypes were 8%, 54%, and 38%, respectively. Patients homozygous for the C allele had higher circulating levels of IL-6 postoperatively than the patients with the CG and GG genotypes (P = .09). Patients homozygous for the G allele had a significantly lower incidence of postoperative atrial fibrillation (P = .032) and a shorter hospital stay (P = .005). This result remained statistically significant following risk stratification. The severity of coronary artery disease and a higher number of bypass grafts were associated with a significant increase in IL-6 level postoperatively (P = .028, and P = .005, respectively). Higher levels of IL-6 were associated with increased blood loss postoperatively (P = .016).
The C allele is associated with higher postoperative IL-6 levels and a less favorable clinical outcome. The G-174C polymorphism is related to the outcome after coronary revascularization.
促炎细胞因子白细胞介素6(IL-6)水平在手术后会升高。IL-6启动子区域的功能性多态性G-174C与冠心病风险增加相关。我们研究了IL-6对冠状动脉血运重建反应的遗传易感性,并探讨了G-174C多态性、IL-6水平与手术临床结局之间的关联。
从96例连续接受择期冠状动脉血运重建的患者中获取DNA。通过序列特异性引物-聚合酶链反应分析对患者进行IL-6 G-174C多态性基因分型。采用酶联免疫吸附测定法在术后3小时采集的血清样本中检测IL-6水平。将IL-6水平和基因型(CC、CG和GG)与围手术期临床数据进行关联分析。
IL-6 -174基因型CC、CG和GG的患病率分别为8%、54%和38%。C等位基因纯合的患者术后IL-6循环水平高于CG和GG基因型的患者(P = 0.09)。G等位基因纯合的患者术后房颤发生率显著较低(P = 0.032),住院时间较短(P = 0.005)。风险分层后该结果仍具有统计学意义。冠状动脉疾病的严重程度和更多的搭桥血管数量与术后IL-6水平显著升高相关(分别为P = 0.028和P = 0.005)。较高的IL-6水平与术后失血增加相关(P = 0.016)。
C等位基因与术后较高的IL-6水平及较差的临床结局相关。G-174C多态性与冠状动脉血运重建后的结局有关。