The aim of this study was to determine the gene–environment interactions of smoking and shared epitope (SE) both separately and combined on anti-cyclic citrullinated peptide (CCP) antibodies in patients with rheumatoid arthritis (RA).Methods:
The literature was searched using the MEDLINE, EMBASE and Cochrane databases. A meta-analysis on the associations between tobacco exposure (TE) and/or SE and the development of anti-CCP antibodies in patients with RA was performed.Results:
Eight comparison studies with 5317 RA patients were considered in this meta-analysis. The odds ratio (OR) for positive anti-CCP antibodies in TE+/SE− patients with RA was increased compared with TE−/SE− patients (OR = 1.373, 95% CI = 1.111–1.698, P = 0.003). The ORs for positive anti-CCP antibodies in TE−/SE+ patients and TE+/SE+ patients with RA were also increased compared with TE−/SE− patients (OR = 2.678, 95% CI = 2.031–3.532, P < 1.0 × 10−9 in TE−/SE+; OR = 4.233, 95% CI = 2.458–7.291, P = 1.9 × 10−8 in TE+/SE+). Stratification by ethnicity indicated the same pattern as that shown in the overall group. The OR for positive anti-CCP antibodies in TE+/SE+ patients with RA was much higher than in TE−/SE− patients in Europeans and Asians (OR = 3.879, 95% CI = 2.203–6.830, P = 2.6 × 10−7; OR = 10.504, 95% CI = 3.182–34.67, P = 1.1 × 10−4).Conclusions:
This meta-analysis suggests a gene–environmental interaction between smoking and SE for the development of anti-CCP antibodies.