A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis
- PMID: 15476204
- DOI: 10.1002/art.20553
A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis
Abstract
Objective: The main genetic risk factor for rheumatoid arthritis (RA) is the shared epitope (SE) of HLA-DR, while smoking is an important environmental risk factor. We studied a potential gene-environment interaction between SE genes and smoking in the etiology of the 2 major subgroups of RA: rheumatoid factor (RF)-seropositive and RF-seronegative disease.
Methods: A population-based case-control study involving incident cases of RF-seropositive and RF-seronegative RA (858 cases and 1,048 controls) was performed in Sweden. Cases and controls were classified according to their cigarette smoking status and HLA-DRB1 genotypes. The relative risk of developing RA was calculated for different gene/smoking combinations and was compared with the relative risk in never smokers without SE genes.
Results: The relative risk of RF-seropositive RA was 2.8 (95% confidence interval [95% CI] 1.6-4.8) in never smokers with SE genes, 2.4 (95% CI 1.3-4.6) in current smokers without SE genes, and 7.5 (95% CI 4.2-13.1) in current smokers with SE genes. Smokers carrying double SE genes displayed a relative risk of RF-seropositive RA of 15.7 (95% CI 7.2-34.2). The interaction between smoking and SE genes was significant, as measured by the attributable proportion due to interaction, which was 0.4 (95% CI 0.2-0.7) for smoking and any SE, and 0.6 (95% CI 0.4-0.9) for smoking and a double SE. Neither smoking nor SE genes nor the combination of these factors increased the risk of developing RF-seronegative RA.
Conclusion: The disease risk of RF-seropositive RA associated with one of the classic genetic risk factors for immune-mediated diseases (the SE of HLA-DR) is strongly influenced by the presence of an environmental factor (smoking) in the population at risk.
Copyright 2004 American College of Rheumatology
Comment in
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Smoking and HLA-DR shared epitope alleles in rheumatoid arthritis: comment on the article by Padyukov et al.Arthritis Rheum. 2005 Nov;52(11):3675-6; author reply 3676-8. doi: 10.1002/art.21504. Arthritis Rheum. 2005. PMID: 16258906 No abstract available.
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The interaction of smoking and the HLA-DRB1 shared epitope in rheumatoid factor-positive rheumatoid arthritis: comment on the article by Padyukov et al.Arthritis Rheum. 2005 Nov;52(11):3676; author reply 3676-8. doi: 10.1002/art.21505. Arthritis Rheum. 2005. PMID: 16258907 No abstract available.
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