title: Gene-environmental interaction between smoking and shared epitope on the development of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: a meta-analysis.
abstract: OBJECTIVE
  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 × 1(0-9) 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.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.forename: Gwan Gyu
authors.initials: GG
authors.lastname: Song
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D000939:Epitopes; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016017:Odds Ratio; D010456:Peptides, Cyclic / Q000276:immunology*; D010641:Phenotype; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: anti-CCP antibodies; rheumatoid arthritis; shared epitope; smoking