Objectives Previous studies on rheumatoid arthritis (RA) and body mass index (BMI) have yielded diverging results. We aimed to clarify the influence of BMI on the risk of developing anticitrullinated peptide antibody (ACPA)-positive and ACPA-negative RA by taking into consideration gender, smoking habits and human leukocyte antigen (HLA-DRB1) shared epitope (SE) status.

Methods The present report is based on a Swedish population-based, case–control study with incident cases of RA (3572 cases, 5772 matched controls). Using logistic regression models, overweight/obese subjects were compared with normal weight subjects regarding risk of developing RA, by calculating ORs with 95% CIs.

Results We observed diverging results for women and men. Among women, the risk of both ACPA-positive and ACPA-negative RA increased with increasing BMI, whereas an inverse association was observed among men for ACPA-positive RA. The results were similar regardless if RA onset before or after the age of 55 years was considered. When the analyses were stratified by smoking habits, the influence of BMI on RA risk was mainly restricted to smokers. Among women, a significant interaction was observed between smoking and overweight/obesity with regard to both subsets of RA. No interaction was observed between HLA-DRB1 SE and overweight/obesity with regard to RA risk.

Conclusions The interaction between smoking and obesity regarding risk for RA in women warrants efforts to reduce these risk factors in those at risk for RA. The sex differences concerning the influence of obesity on RA risk merit further studies to verify these results and understand underlying mechanisms.