Interleukin-6 gene -174G > C and -572G > C promoter polymorphisms are strong predictors of plasma - Interleukin-6 levels after coronary artery bypasssurgery

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. W e have examined the effect of common polymorphisms in the IL-6 gene promote r (-1746>C, -572G>C, and -5976>A) on IL-6 levels after elective CABG. DNA e xtracted from the peripheral blood of 127 patients was amplified by polymer ase chain reaction. IL-6 genotypes were resolved by gel electrophoresis aft er restriction enzyme digestion. Serum IL-6 was measured before surgery and in serial samples at 6, 24, 48, and 72 hours after CABG. Genotype distribu tion 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 -1740 0.37 (0.31 to 0.43). The -1746>C and -5976>A genotypes were in st rong allelic association (Delta =0.97, P<0.001). Baseline IL-6 levels did n ot significantly differ between patients with different genotypes for any p olymorphism. However, 6 hours after CABG, peak IL-6 levels were significant ly higher (P=0.03) in carriers of the -572C allele than in those of the -57 2GG genotype (355 +/- 67 versus 216 +/- 13 pg/mL, respectively) and in thos e with genotype -174CC compared with -174G allele carriers (287 +/- 31 vers us 227 +/- 15 pg/mL, respectively; P=0.04). These effects remained statisti cally 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 po lymorphisms influence peak IL-6 production after CABG, suggesting that thes e polymorphisms, which are functional in vitro, are also functional in vivo , suggesting a genetic influence on IL-6 levels after acute severe injury.