Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1458-1463
doi: 10.1161/hq0901.094280
doi: 10.1161/hq0901.094280
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Interleukin-6 Gene -174G>C and -572G>C Promoter Polymorphisms Are Strong Predictors of Plasma Interleukin-6 Levels After Coronary Artery Bypass Surgery
From the Division of Cardiovascular Genetics, Department of Medicine (D.J.B., H.E.M., J.S., S.D., L.L., S.E.H.), Royal Free and University College London Medical School, London, UK, and the Department of Medicine (A.R., G.D.O.L.), University of Glasgow, Glasgow, UK.
Correspondence to Dr D.J. Brull, Division of Cardiovascular Genetics, Rayne Institute, 5 University St, London WC1E 6JJ, UK. E-mail d.brull{at}ucl.ac.uk
Abstract—— Interleukin-6 (IL-6) synthesized in response to diverse stimuli may play an important role in bridging the inflammatory and atherosclerotic processes. The acute-phase response after coronary artery bypass graft surgery (CABG) is associated with the induction and release of cytokines, such as IL-6. We have examined the effect of common polymorphisms in the IL-6 gene promoter (-174G>C, -572G>C, and -597G>A) on IL-6 levels after elective CABG. DNA extracted from the peripheral blood of 127 patients was amplified by polymerase chain reaction. IL-6 genotypes were resolved by gel electrophoresis after restriction enzyme digestion. Serum IL-6 was measured before surgery and in serial samples at 6, 24, 48, and 72 hours after CABG. Genotype distribution was as expected for a population in Hardy-Weinberg equilibrium for all polymorphisms. Rare allele frequencies (±95% CIs) were similar to those reported previously: -597A 0.36 (0.30 to 0.42), -572C 0.07 (0.04 to 0.10), and -174C 0.37 (0.31 to 0.43). The -174G>C and -597G>A genotypes were in strong allelic association (
=0.97, P<0.001). Baseline IL-6 levels did not significantly differ between patients with different genotypes for any polymorphism. However, 6 hours after CABG, peak IL-6 levels were significantly higher (P=0.03) in carriers of the -572C allele than in those of the -572GG genotype (355±67 versus 216±13 pg/mL, respectively) and in those with genotype -174CC compared with -174G allele carriers (287±31 versus 227±15 pg/mL, respectively; P=0.04). These effects remained statistically significant after adjusting for possible confounders, including age, sex, smoking, duration of cardiopulmonary bypass, aortic cross-clamp time, and total duration of surgery. These data demonstrate that IL-6 promoter polymorphisms influence peak IL-6 production after CABG, suggesting that these polymorphisms, which are functional in vitro, are also functional in vivo, suggesting a genetic influence on IL-6 levels after acute severe injury.
Key Words: interleukin-6 • genetic polymorphism • inflammation • coronary artery bypass surgery
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