The Relationship Between Serum Concentration of Interleukin-35 and FoxP3 Polymorphism in Patients Undergoing Coronary Artery Bypass Graft Surgery

Abstract Objective: To investigate the association between interleukin-35 (IL-35) levels and single nucleotide polymorphisms (rs3761548, rs3761547) of the FoxP3 gene in coronary artery bypass grafting (CABG) patients. Methods: We conducted a prospective study including 140 patients, who were scheduled for elective isolated on-pump CABG with cardiopulmonary bypass (CPB) from January 2017 to September 2018 in the Jorjani heart center. Blood samples were collected before and 12 hours after the operation. Serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the pattern of genetic variations was assessed using single specific primer-polymerase chain reaction. Results: The serum concentrations of IL-35 after surgery were significantly higher than pre-surgery levels (18.4±8.3 vs. 9.89±3.2, respectively, P=0.002). There was no significant association between genotype frequencies of rs3761548 and rs3761547 and elevated IL-35 levels (P>0.05). There were significant associations between IL-35 levels and preoperative variables, including age (r=-0.34, P=0.047) and body mass index (r=-0.41, P=0.045), and intraoperative variables, including CPB time (r=0.4, P=0.02) and mean arterial pressure (r=-0.38, P=0.046), in carriers of the rs3761548 AA genotype. Conclusion: Serum IL-35 concentrations were significantly increased in CPB patients, which may contribute to the post-CPB compensatory anti-inflammatory response syndrome. IL-35 increased levels were not influenced by FoxP3 promoter polymorphisms (rs3761548, rs3761547).

摘要 目的：探讨冠状动脉旁路移植术（coronary artery bypass grafting, CABG）患者外周血白细胞介素-35（interleukin-35, IL-35）水平与叉头框P3基因（FoxP3）单核苷酸多态性位点rs3761548、rs3761547的关联。方法：本研究为前瞻性研究，纳入2017年1月至2018年9月于约尔贾尼心脏中心行择期单纯体外循环（cardiopulmonary bypass, CPB）下冠状动脉旁路移植术的140例患者。分别于术前及术后12小时采集血液样本；采用酶联免疫吸附试验检测血清IL-35水平，通过单特异性引物聚合酶链式反应分析基因变异分型。结果：术后血清IL-35浓度显著高于术前水平（分别为18.4±8.3与9.89±3.2，P=0.002）。rs3761548与rs3761547的基因型频率与IL-35水平升高无显著相关性（P>0.05）。在rs3761548 AA基因型携带者中，IL-35水平与术前变量[年龄（r=-0.34，P=0.047）、体质量指数（r=-0.41，P=0.045）]及术中变量[体外循环时间（r=0.4，P=0.02）、平均动脉压（r=-0.38，P=0.046）]存在显著关联。结论：体外循环患者术后血清IL-35浓度显著升高，这可能参与体外循环后代偿性抗炎反应综合征的发生发展；IL-35水平升高不受FoxP3启动子多态性位点rs3761548、rs3761547的影响。