Interleukin 6 G-174C Polymorphism Influences Outcome Following Coronary Revascularization Surgery
DOI:
https://doi.org/10.1532/HSF98.20041120Abstract
Background: 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.
Methods: 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.
Results: 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)
Conclusions: 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.
References
Humphries SE, Luong LA, Ogg MS, Hawe E, Miller GJ. 2001. The interleukin-6 -174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 22:2243-52.nJenny NS, Tracy RP, Ogg MS, et al. 2002. In the elderly, interleukin-6 plasma levels and the -174G>C polymorphism are associated with the development of cardiovascular disease. Arterioscler Thromb Vasc Biol 22:2066-71.nJones KG, Brull DJ, Brown LC, et al. 2001. Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation 103:2260-5.nLiebold A, Langhammer T, Brunger F, Birnbaum DE. 1999. Cardiac interleukin-6 release and myocardial recovery after aortic crossclamping: crystalloid versus blood cardioplegia. J Cardiovasc Surg (Torino) 40:633-6.nMisoph M, Babin-Ebell J. 1997. Interindividual variations in cytokine levels following cardiopulmonary bypass. Heart Vessels 12:119-27.nMorrow DA, Ridker PM. 2000. C-reactive protein, inflammation, and coronary risk. Med Clin North Am 84:149-61, ix.nPannen BH, Robotham JL. 1995. The acute-phase response. New Horiz 3:183-97.nAbe K, Nishimura M, Sakakibara T. 1994. Interleukin-6 and tumournecrosis factor during cardiopulmonary bypass. Can J Anaesth 41:876-7.nBaeuerle PA, Rupec RA, Pahl HL. 1996. Reactive oxygen intermediates as second messengers of a general pathogen response. Pathol Biol (Paris) 44:29-35.nBasso F, Lowe GD, Rumley A, McMahon AD, Humphries SE. 2002. Interleukin-6 -174G>C polymorphism and risk of coronary heart disease in West of Scotland Coronary Prevention Study (WOSCOPS). Arterioscler Thromb Vasc Biol 22:599-604.nBrull DJ, Montgomery HE, Sanders J, et al. 2001. Interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 21:1458-63.nWei M, Kuukasjarvi P, Laurikka J, et al. 2001. Cytokine responses in patients undergoing coronary artery bypass surgery after ischemic preconditioning. Scand Cardiovasc J 35:142-6.nBurzotta F, Iacoviello L, Di Castelnuovo A, et al. 2001. Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization. Am J Cardiol 88:1125-8.nButler J, Baigrie RJ, Parker D, et al. 1993. Systemic inflammatory responses to cardiopulmonary bypass: a pilot study of the effects of pentoxifylline. Respir Med 87:285-8.nFinkel MS, Hoffman RA, Shen L, et al. 1993. Interleukin-6 (IL-6) as a mediator of stunned myocardium. Am J Cardiol 71:1231-2.nGaudino M, Andreotti F, Zamparelli R, et al. 2003. The -174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation: is atrial fibrillation an inflammatory complication? Circulation 108(suppl 1):II-195-9.nGaudino M, Di Castelnuovo A, Zamparelli R, et al. 2003. Genetic control of postoperative systemic inflammatory reaction and pulmonary and renal complications after coronary artery surgery. J Thorac Cardiovasc Surg 126:1107-12.nGiomarelli P, Scolletta S, Borrelli E, Biagioli G. 2003. Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10. Ann Thorac Surg 76:117-23.nPapanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP. 1998. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 128:127-37.nPerrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV. 1999. ARMS-PCR methodologies to determine IL-10, TNF-alpha, TNF-beta and TGF-beta 1 gene polymorphisms. Transpl Immunol 7:127-8.nRidker PM, Hennekens CH, Buring JE, Rifai N. 2000. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342:836-43.nRidker PM, Rifai N, Stampfer MJ, Hennekens CH. 2000. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767-72.nRothenburger M, Soeparwata R, Deng MC, et al. 2001. Prediction of clinical outcome after cardiac surgery: the role of cytokines, endotoxin, and anti-endotoxin core antibodies. Shock 16(suppl 1):44-50.nSpeziale G, Ferroni P, Ruvolo G, et al. 2000. Effect of normothermic versus hypothermic cardiopulmonary bypass on cytokine production and platelet function. J Cardiovasc Surg (Torino) 41:819-27.n
