Smoking is associated with an increased risk of developing ACPA-positive but not ACPA-negative rheumatoid arthritis in Asian populations: evidence from the Malaysian MyEIRA case-control study

Mod Rheumatol. 2012 Aug;22(4):524-31. doi: 10.1007/s10165-011-0544-2. Epub 2011 Oct 18.


We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18-70 years within a defined area of Peninsular Malaysia were evaluated in a case-control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9-9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3-2.0), compared with never-smokers. A significant dose-response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1-9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6-17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / ethnology
  • Arthritis, Rheumatoid / etiology*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Case-Control Studies
  • China / ethnology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • India / ethnology
  • Malaysia / epidemiology
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Risk Assessment
  • Smoking / adverse effects*
  • Surveys and Questionnaires
  • Time-to-Treatment


  • Autoantibodies
  • Peptides, Cyclic
  • cyclic citrullinated peptide