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  • Title: Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: the role of obesity and smoking.
    Author: Panoulas VF, Stavropoulos-Kalinoglou A, Metsios GS, Smith JP, Milionis HJ, Douglas KM, Nightingale P, Kitas GD.
    Journal: Atherosclerosis; 2009 May; 204(1):178-83. PubMed ID: 18848327.
    Abstract:
    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-6-174 G/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.
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