Abstract

Cigarette smoking has been shown in European populations to be associated with rheumatoid arthritis (RA) susceptibility. This study aims to examine the association of smoking with RA in the Han Chinese population. 718 Han Chinese RA patients and 404 healthy controls were studied. The associations of cigarette smoking (current, former or ever vs. never smokers, and pack-years of exposure) with RA, anti-cyclic citrullinated peptide antibody (ACPA) positive RA, IgM rheumatoid factor (RF) positive RA, and baseline radiographic erosions (modified van der Heijde-Sharp scores) were assessed. The interaction between smoking and the HLA-DRB1 shared epitope (SE) in RA was also examined. In this study, 11 (1.53%) cases and 6 (1.49%) controls were former smokers (p = 0.95), while 95 (13.23%) cases and 48 (11.88%) controls were current smokers (p = 0.52). Trends toward associations between smoking status (ever vs. never) with RA-overall (p = 0.15, OR = 1.44), ACPA-positive RA (p = 0.24, OR = 1.37), RF-positive RA (p = 0.14, OR = 1.46), or the presence of radiographic erosions (p = 0.66, OR = 1.28) were observed although individually here were not statistically significant. There was no evidence of statistical interaction between smoking status (ever vs. never) and SE for all RA, ACPA-positive RA, ACPA-negative RA, RF-positive RA, RF-negative RA (p = 0.37, 0.50, 0.24, 0.26, and 0.81 respectively), and the 95% CI for the attributable proportion for all interactions included 0. This is the first study to examine the association of cigarette smoking with RA in the Han Chinese population. This study shows a trend toward an interaction between smoking and SE carriage influencing the risk of RA, though findings were not statistically significant. It is possible that in the presence of universal exposure to heavy air pollution the effect of smoking on RA risk may be obscured.

Highlights

  • Rheumatoid arthritis (RA) is a complex immune-mediated disease that is thought to arise due to the interacting effects of environmental and genetic factors

  • Cases and controls were well matched for gender (77.44 vs. 75.74% female, p = 0.52), but RA cases were older than controls (53.19 vs. 44.56 years, p < 0.01)

  • The differences of shared epitope (SE) subtypes between two groups were shown in Table 2. 566 (78.83%) and 574 (79.94%) cases were anti-cyclic citrullinated peptide antibody (ACPA) and rheumatoid factor (RF)-positive, respectively. 462 cases (89.36%) had baseline radiographic erosions. 11 (1.53%) cases and 6 (1.49%) controls were former smokers while 95 (13.23%) cases and 48 (11.88%) controls were current smokers

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Summary

Introduction

Rheumatoid arthritis (RA) is a complex immune-mediated disease that is thought to arise due to the interacting effects of environmental and genetic factors. Several studies performed in populations of European ancestry have suggested that smoking is an environmental risk factor increasing the risk of RA [1,2,3]. Several studies have reported that smoking interacts with HLA-DRB1 in increasing the risk of anti-cyclic citrullinated peptide antibody (ACPA)-positive, but not ACPA-negative, RA [5,6,7]. This suggests that the pathogenesis of ACPA-positive RA might differ from that of ACPA-negative disease [8], the extensive sharing of genetic associations between the two subtypes of RA [9] indicates that they have marked similarity of genetic architecture.

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