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A-203
2004 |
| Effect of Interleukin-6 Promoter Polymorphism (-174 G/C) on Systemic Interleukin-6 Levels and Long-Term Survival Following Cardiopulmonary Bypass |
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Stefan P. Wirtz, M.D., Berhard Schlüter, M.D., Hugo Van Aken, M.D., Ph.D., Marion Scharte, M.D., Elmar Berendes, M.D., Ph.D. Anesthesiology and Intensive Care Medicine, University Hospital Münster, Münster, Germany. |
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Introduction: Interleukin (IL)-6 plasma levels closely correlate with the severity of systemic inflammatory response for example following cardiopulmonary bypass (CPB) and sepsis. A biallelic polymorphism within the human IL-6 gene promoter region (-174 G/C) seems to affect the IL-6 response to inflammation: The GG homozygous genotype is associated with a lower increase of IL-6 levels after coronary artery bypass grafting1 and improved survival rates in sepsis2. We investigated the effect of the IL-6 promoter polymorphism (-174 G/C) on systemic IL-6 plasma levels and long-term survival following CPB. Method: After approval by the local ethic committee and informed consent from each patient, a total of 120 cardiac surgical patients were prospectively enrolled. Sex-matched healthy volunteers of the same ethnic origin served as control group. Venous EDTA-anticoagulated blood samples for IL-6 level measurements using ELISA were collected preoperatively, 20 minutes after onset of CPB and 4, 8, 12, 24, 48 and 72 hours after admission to the ICU. Genotyping of leucocyte DNA was performed with the mutagenically separated polymerase chain reaction (MS-PCR) developed by Rust and colleagues3. Chi²- and Kruskal-Wallis-Tests were used for statistical analysis. Results: 120 patients (92 male /28 female; age: 64 ± 9.7 yrs.; 85 CABG; 35 valve replacement) were investigated. Fourteen patients died within a two year period after the procedure. Genotype distribution and allele frequencies in patients and healthy controls did not differ significantly. There was no significant difference in preoperative IL-6 plasma levels of patients with different genotypes. However, -174GG homozygous genotype was associated with a lower initial increase of IL-6 plasma levels (p = 0.02; GG versus GC/CC; Fig. 1) and a higher survival rate within a two years period after the procedure (OR 0.13 (0.02-1.0); p = 0,049; Fig. 2) compared to carrier of the -174C allele (genotype -174 GC and -174 CC). Conclusion: The IL-6 promoter polymorphism (-174 G/C) is associated with the increase of systemic IL-6 plasma concentrations and long-term survival following procedures with CPB. Homozygous GG-genotype carrier seem to have a higher chance of survival and a reduced inflammatory response after CPB compared to -174 C-allele carrier. References: 1. Arterioscler Thromb Vasc Biol 2001; 21:1458-1463 2. Crit Care Med 2002; 30:32-37. 3. Nucleic Acids Res 1993; 21:3623-3629. Anesthesiology 2004; 101: A203 |
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