rss
Ann Rheum Dis 2006;65:1163-1167 doi:10.1136/ard.2005.049676
  • Extended report

Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian women

  1. L A Criswell1,
  2. K G Saag2,
  3. T R Mikuls3,
  4. J R Cerhan4,
  5. L A Merlino5,
  6. R F Lum1,
  7. K A Pfeiffer1,
  8. B Woehl6,
  9. M F Seldin6
  1. 1Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, USA
  2. 2Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, USA
  3. 3Section of Rheumatology and Omaha VA Medical Center, University of Nebraska, Omaha, USA
  4. 4Department of Epidemiology, Mayo Clinic College of Medicine, Rochester, USA
  5. 5College of Public Health, University of Iowa, Iowa City, USA
  6. 6Rowe Program in Human Genetics, University of California, Davis, USA
  1. Correspondence to:
    Professor L A Criswell
    Division of Rheumatology, University of California, San Francisco, 374 Parnassus Avenue, Box 0500, San Francisco, CA 94143-0500, USA; Lindsey.Criswell{at}ucsf.edu
  • Accepted 17 June 2006
  • Published Online First 3 August 2006

Abstract

Objective: To determine whether the impact of tobacco exposure on rheumatoid arthritis (RA) risk is influenced by polymorphisms at the HLA-DRB1 and glutathione S-transferase M1 (GSTM1) loci.

Methods: Subjects were participants from a case-control study nested within the Iowa Women’s Health Study, a population based, prospective cohort study of postmenopausal women. Incident RA cases (n = 115) were identified and medical records reviewed to confirm RA diagnosis. Controls without RA (n = 466) were matched with RA cases by age and ethnic background. HLA-DRB1 typing classified subjects according to the presence of alleles encoding the RA “shared epitope” (SE) sequence. GSTM1 was genotyped using a multiplex polymerase chain reaction assay. Conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals.

Results: Strong positive associations of smoking (OR = 6.0, p = 0.004), SE positivity (OR = 4.6, p = 0.0006), and GSTM1 null genotype (OR = 3.4, p = 0.007) with risk of RA, and significant gene-environment interactions (smoking by SE interaction p = 0.034; smoking by GSTM1 interaction p = 0.047) were observed. Stratified analyses indicated that exposure to tobacco smoke primarily increased the risk of RA among subjects who lacked genetic risk factors for the disease (that is, SE negative or GSTM1 present).

Conclusions: Although these findings require confirmation in other groups, the results support the importance of considering both genetic and environmental factors, and also their interaction, in studies of complex diseases like RA.

Footnotes

  • Competing interests: None.

This Article

  1. Abstract
  2. Full text
  3. PDF
  4. All versions of this article:
    1. ard.2005.049676v1
    2. 65/9/1163 most recent

Responses

  1. Submit a response
  2. No responses published

Register for free content

The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.

Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.