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THU0008 Meta-analysis of the association of smoking and PTPN22 R620W genotype on autoantibody status and radiological erosions in rheumatoid arthritis
  1. L.H. Taylor1,
  2. S. Twigg2,
  3. J.J. Worthington3,
  4. P. Emery2,
  5. A.W. Morgan2,
  6. A.G. Wilson4,
  7. M.D. Teare1
  8. and UKRAGG
  1. 1School of Health and Related Research, Sheffield University, Sheffield
  2. 2NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds
  3. 3Musculoskeletal Research Group, University of Manchester, Manchester Academic Health Sciences Centre, Manchester
  4. 4Department of Infection and Immunity, The University of Sheffield Medical School, Sheffield, United Kingdom

Abstract

Background Smoking has been linked to production of anti-citrullinated protein antibodies (ACPA) in HLA-DRB1 shared epitope positive patients which has also been associated with a worse severity of rheumatoid arthritis (RA) [1, 2]. In addition, a single amino acid change R620W (rs2476601) in the protein tyrosine phosphatase non-receptor 22 (PTPN22) has been found to interact with smoking and ACPA positivity [3].

Despite this, a recent study [4] (N=532) found no evidence that smoking increased the risk of being ACPA positive. In addition, they reported a protective effect of smoking on the development of bone erosions in subjects who had ever smoked (OR=0.44, 95%CI 0.3-0.7, P≤0.0001) and a larger protective effect when subjects ever smoked in combination with carrying at least one of the PTPN22 single amino acid changes R620W (rs2476601) (OR=0.25, 95%CI 0.1-0.6, P=0.002) [4].

Objectives To investigate the inter-relationships between smoking, protein tyrosine phosphatase non-receptor 22 (PTPN22) R620W genotype and anti-citrullinated peptide antibodies (ACPA) status and to investigate the inter-relationships between smoking, PTPN22 R620W genotype and presence of bone erosions in patients with RA.

Methods Six studies totalling 2680 RA patients were included in a Mantel-Haenszel fixed effects meta-analysis investigating ACPA status and eight studies totalling 3172 RA patients were included in a Mantel-Haenszel fixed effects meta-analysis investigating presence of erosive damage.

Results Evidence was found for an increase in the odds of ACPA positivity for ever smoking (OR=1.56, 95%CI 1.28-1.90, p=8.5 ×10-6), carriage of at least one of the PTPN22 risk alleles (OR=1.50, 95%CI 1.13-2.00, P=0.0055) and both ever smoking and carriage of at least one of the PTPN22 risk alleles (OR=2.22, 95%CI 1.69-2.91, P=8.3×10-9). There was no evidence of an association between presence of erosive damage and smoking status or carriage of PTPN22 risk alleles.

Conclusions This meta-analysis indicates that both smoking and having the PTPN22 risk allele affect the risk of ACPA positivity, however, neither PTPN22 nor smoking is associated with erosive damage.

  1. Baka Z, Buzas E, Nagy G. Rheumatoid arthritis and smoking: putting the pieces together. Arthritis Research & Therapy. 2009; 11(4).

  2. Lee DM, Phillips R, Hagan EM, Chibnik LB, Costenbader KH, Schur PH. Quantifying anti-cyclic citrullinated peptide titres: clinical utility and association with tobacco exposure in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2009; 68(2):201-208.

  3. Morgan AW, Thomson W, Martin SG, Carter AM, Erlich HA, Barton A, et al. Reevaluation of the Interaction Between HLA-DRB1 Shared Epitope Alleles, PTPN22, and Smoking in Determining Susceptibility to Autoantibody-Positive and Autoantibody-Negative Rheumatoid Arthritis in a Large UK Caucasian Population. Arthritis and Rheumatism. 2009; 60(9):2565-2576.

  4. Salliot C, Dawidowicz K, Lukas C, Guedj M, Paccard C, Benessiano J, et al. PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort. Rheumatology. 2011; 50(10):1802-1808.

Disclosure of Interest None Declared

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