Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: The role of obesity and smoking

Background: Cardiovascular morbidity and mortality are increased in rheumatoid arthritis (RA). Interleukin-6 (IL-6) is high in RA and, together with smoking and obesity, an important contributor to the development of cardiovascular disease (CVD). The present study examined the potential association of IL-6-174G/C polymorphism, together with obesity and smoking, with the presence of CVD in RA patients. Methods and results: DNA samples were collected from 383 RA patients (who also had extensive clinical and laboratory evaluations). IL-6-174 G/C was identified using real time PCR and melting curve analysis. Serum IL-6 levels were measured in a subgroup of 135 RA patients to examine the functionality of the polymorphism. Carriers of the IL6-174C-allele demonstrated increased prevalence of CVD (26.2% vs. 17.0%, p = 0.041). There was a significant association with CVD, even after adjustment for traditional CVD risk factors (OR = 1.92,95%CI: 1.03 to 3.58, p = 0,041). IL-6 levels were significantly increased in C-allele carriers [14.02 (3,21-38.81) vs. 4.48 (2.25-16.5), p = 0.028]. No significant interactions were observed between adiposity and IL6-174G/C genotypes. There was only a trend for an interaction between ever smoking and IL6 C-allele carriers on CVD. Conclusion: The IL-6-174C-allele may associate with CVD in RA patients and possibly exerts its effect via increased inflammation. This finding, if confirmed in future studies, may be used as a part of a genetic screening tool for RA patients at high CVD risk. (C) 2008 Elsevier Ireland Ltd. All rights reserved.