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-6-174 G/C polymorphism, together with obesity and smoking, with the presence of CVD in RA patients.


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.


CONCLUSIONS
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.
Panoulas
Vasileios F
VF
Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, West Midlands, UK.
Stavropoulos-Kalinoglou
Antonios
A
Metsios
Giorgos S
GS
Smith
Jacqueline P
JP
Milionis
Haralampos J
HJ
Douglas
Karen M J
KM
Nightingale
Peter
P
Kitas
George D
GD
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000453:epidemiology; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology
C508600:IL6 protein, human; D015850:Interleukin-6