Abstract 16562: Effects of the G174C Polymorphism in Interleukin-6 Gene Promoter on Inflammatory and Thrombotic Processes and in severity of Coronary Artery Disease in Patients With Advanced Atherosclerosis
Background: Interleukin-6 (IL-6) represents an early marker of inflammatory activation, strongly related to the pathophysiology of coronary artery disease (CAD). However, it remains unclear, whether common polymorphisms within the IL-6 gene affect the mechanisms of CAD. In the present study we examined the impact of the G174C polymorphism on IL-6 gene promoter on inflammatory and thrombotic processes and on the severity of CAD.
Methods: The study population consisted of 360 patients with angiographically documented CAD and 282 healthy controls. The G174C polymorphism was determined by PCR and digestion with SFA NI restriction enzyme. High sensitivity C-Reactive Protein (hsCRP) (mg/dl) and D-dimers (pg/l) were determined with immunonephelometry, while fibrinogen (mg/dl) with the von Clauss method. IL-6 (pg/ml) and sCD40L (pg/ml) were assessed by ELISA.
Results: The genotype distribution was: GG: 42.1 %, GC: 41.5%, CC: 16.4% in CAD and GG: 44.3%, GC: 42.1%, CC: 13.6% in controls. Although CC genotype presented a borderline positive trend compared to G carriers regarding the incidence (p=0.07) and severity of CAD (1 vessel vs 2+3 vessels R.R.: 1.091, 95% C. I.: 0.9962-1.194, p=0.07), the difference was not significant. Similarly, CC genotype was not related with levels of fibrinogen (450.26±131.23 vs 446.88±135.33, p=NS), sCD40L (2.146±1.388 vs 2.3±2.29, p=NS) and D-dimers (451.45±286.05 vs 458.83± 296.04, p=NS) not only in CAD, but also in controls (fibrinogen: 368.78±93.579 vs 379.62±100.68, sCD40L: 0.825±0.802 vs 1.121±1.026, D-dimers: 383.85±325.26 vs 366.54±295.8, p=NS for all). Importantly, CC homozygotes were related with significantly higher serum levels of IL-6 and hsCRP compared to GG homozygotes in CAD (4.654±0.918 vs 2.633±1.187 and 2.867±0.87 vs 2.130±0.662, respectively, p<0.001), and in controls as well (2.131±0.27 vs 1.314±0.518 and 1.654±0.406 vs 0.98±0.482, respectively, p<0.001).
Conclusions: We have found that the G174C polymorphism on Interleukin-6 gene promoter does not alter the coagulation status. On the contrary, CC homozygosity increases significantly the inflammatory process of both subjects with and without advanced atherosclerosis.
- © 2013 by American Heart Association, Inc.