Interaction between oxidative stress and smoking is associated with an increased risk of rheumatoid arthritis: a case–control study

Objective. To investigate the relationship between oxidative stress and smoking and development of RA. Methods. A casecontrol study was conducted in treatment-naive early-onset RA patients and healthy controls, matched by age, gender and current smoking habit. Plasma lipid hydroperoxides (LOOH), car- bonyl protein (CP) and malonyldialdehyde (MDA) levels were measured to estimate oxidative stress. Smoking exposure was quantified in pack-years. The presence of an interaction between oxidative stress and smoking exposure was investigated using three measures of additive interaction: relative excess risk due to the interaction (RERI), attributable proportion due to the interaction (AP) and the synergy index (S). Results. A total of 65 RA patients and 65 healthy controls were included. Statistically significant differ- ences were observed in RA-related variables, age, BMI and smoking dose between cases and controls. Plasma LOOH and CP levels were associated with RA risk, which was more prominent for LOOH levels >27.9mM (odds ratio (OR) 18.8) and CP levels >64.3 mM (OR 24.9). A reverse association was observed between MDA levels and RA risk, OR 6.4 for MDA levels 20 pack-years increased risk for RA with an OR of 19.7. The interaction between smoking and oxidative stress increased RA risk significantly, and RERI between LOOH, CP or MDA and smoke exposure were 8.2, 5.0 and 51.5, respectively. Conclusion. These data suggest that the interaction between oxidative stress and smoking increases RA risk.