Interactions between HLA and PTPN22 genotypes and smoking have been implicated in overall susceptibility to rheumatoid arthritis as well as the incidence of particular disease phenotypes in case–control and case-only studies. As recent epidemiological evidence shows, deciphering these interactions demands consideration of the analytical approach used.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Costenbader, K. H., Feskanich, D., Mandl, L. A. & Karlson, E. W. Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am. J. Med. 119, 503–511 (2006).
Morgan, A. W. 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 Rheum. 60, 2565–2576 (2009).
Rothman, K. J. Epidemiology: an Introduction (Oxford University Press, New York, 2002).
Padyukov, L., Silva, C., Stolt, P., Alfredsson, L. & Klareskog, L. A gene–environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 50, 3085–3092 (2004).
Klareskog, L. et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 54, 38–46 (2006).
Hill, J. A. et al. Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J. Immunol. 171, 538–541 (2003).
Karlson, E. W. et al. Gene–environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis. Ann. Rheum. Dis. 69, 54–60 (2010).
Linn-Rasker, S. P. et al. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann. Rheum. Dis. 65, 366–371 (2006).
Lee, H. S. et al. Interaction between smoking, the shared epitope, and anti-cyclic citrullinated peptide: a mixed picture in three large North American rheumatoid arthritis cohorts. Arthritis Rheum. 56, 1745–1753 (2007).
Kallberg, H. et al. Gene–gene and gene–environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am. J. Hum. Genet. 80, 867–875 (2007).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Karlson, E., Costenbader, K. Interpreting studies of interactions between RA risk factors. Nat Rev Rheumatol 6, 72–73 (2010). https://doi.org/10.1038/nrrheum.2009.276
Issue Date:
DOI: https://doi.org/10.1038/nrrheum.2009.276
This article is cited by
-
Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction
Nature Reviews Rheumatology (2018)