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OBJECTIVE: To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association. METHODS: We conducted a frequency matched case-control study; subjects comprised 515 patients (participation rate 83%) attending rheumatology and internal medicine departments in Denmark, with recently diagnosed RA according to the American College of Rheumatology (ACR) 1987 classification criteria for RA (mean disease duration 2.3 yrs), and 769 frequency-matched population controls (participation rate 64%). Information about SES and environmental exposure was obtained by structured telephone interview. Logistic regression analyses evaluated the role of markers of SES. RESULTS: Level of education was significantly inversely associated with risk of RA, with a 2-fold lower risk of RA among those with the longest formal education compared with those having the lowest level of education (multivariate odds ratio = 0.43, 95% confidence interval 0.24-0.76, p trend = 0.001). None of a series of studied lifestyle factors could explain this finding in multivariate logistic regression analyses. When dividing the RA cases into clinical subgroups, the inverse association with level of education was found to apply predominantly to rheumatoid factor (RF)-positive RA. CONCLUSION: The inverse association between level of education and risk of RF-positive RA was not explained by any of the examined lifestyle factors. RF-positive and RF-negative RA may be 2 distinct diseases with different etiologies, with unmeasured factors related to educational level predominantly associated with the risk of RF-positive RA. However, because mechanisms underlying referral to a hospital might be linked to educational level, our observation based on hospital-referred RA patients should be evaluated cautiously. The study stresses the importance of taking SES measures into account in studies that aim at identifying environmental risk factors for RA.