Background Physical workloads and physical activities/exercises differ in quantity, intensity and duration of mechanical stress exerted on the joint and synovia. There are various types of repetitive prolonged physical workload (RPPW) that have been hypothesized to provide stress to the joints and possibly influence the development of arthritis. To our knowledge, there is no study that investigates the association of various types of RPPW and risk of rheumatoid arthritis (RA).
Objectives To investigate the association between exposure to 7 different types of RPPW and risk of rheumatoid arthritis; to study the potential interactions between different RPPWs and the genes in the human leukocyte antigen (HLA) region.
Methods Data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA), a population-based case-control study involving incident cases of RA (3680 cases and 5935 controls), were analyzed. Information on different types of self-reported RPPW exposures (see figure 1), anti-citrullinated protein antibody (ACPA) status and HLA-DRB1 genotypes of cases and controls were retrieved. RPPW exposed subjects were compared with that of unexposed subjects. Odds ratios (ORs) with 95% confidence intervals (CI) of RA (overall), ACPA-positive RA and ACPA-negative RA associated with various RPPW exposures were estimated using an unconditional logistic regression model. Age, sex, residential area, smoking status, alcohol consumption, body mass index and education were considered as potential confounders and added as covariates in the statistical model. RPPW-HLA interactions were evaluated using the principle of departure from additivity of effects, by calculating the attributable proportion (AP) due to interaction.
Results As shown on figure 1, the estimated ORs of developing RA associated with various RPPW exposures ranged from 1.3 (95% CI, 1.1–1-4) to 1.8 (95%CI, 1.6–2.0). No major difference in the ORs between ACPA-positive and ACPA-negative RA was found. Significant interactions between RPPW exposures and HLA-DRB1 shared epitope genes were observed among ACPA-positive RA (AP values ranging from 0.3 (95% CI, 0.1–0.5) to 0.4 (95%CI, 0.2–0.6)).
Conclusions Repetitive prolonged physical workload (RPPW) is associated with the risk of both ACPA-positive and ACPA-negative RA. The interactions between some RPPWs and HLA-DRB1 shared epitope may be involved in the etiology of ACPA-positive RA.
Acknowledgement The authors thank the investigators and participants from the EIRA study. The authors also thank Marie-Louise Serra and Lena Nise for data collection and Lena Israelsson for performing ELISA analysis.
Disclosure of Interest None declared