Gene–environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis
Open Access
- 16 January 2009
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 69 (01), 54-60
- https://doi.org/10.1136/ard.2008.102962
Abstract
Background: Previous studies have reported an interaction between ever cigarette smoking and the presence of the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype and rheumatoid arthritis (RA) risk. To address the effect of dosage, a case-control study nested within two prospective cohorts to determine the interaction between heavy smoking and the HLA-SE was conducted. Methods: Blood was obtained from 32 826 women in the Nurses’ Health Study and 29 611 women in the Nurses’ Health Study II. Incident RA diagnoses were validated by chart review. Controls were matched for age, menopausal status and postmenopausal hormone use. High-resolution HLA-DRB1 genotyping was performed for SE alleles. HLA-SE, smoking, HLA-SE* smoking interactions and RA risk, were assessed using conditional logistic regression models, adjusted for age and reproductive factors. Additive and multiplicative interactions were tested. Results: In all, 439 Caucasian matched pairs were included. Mean age at RA diagnosis was 55.2 years; 62% of cases were seropositive. A modest additive interaction was observed between ever smoking and HLA-SE in seropositive RA risk. A strong additive interaction (attributable proportion due to interaction (AP) = 0.50; p10 pack-years) and any HLA-SE in seropositive RA risk. The highest risk was in heavy smokers with double copy HLA-SE (odds ratio (OR) 7.47, 95% CI 2.77 to 20.11). Conclusions: A strong gene–environment interaction was observed between HLA-SE and smoking when stratifying by pack-years of smoking rather than by ever smoking. Future studies should assess cumulative exposure to cigarette smoke when testing for gene–smoking interactions.Keywords
This publication has 35 references indexed in Scilit:
- Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cellsAnnals Of The Rheumatic Diseases, 2008
- Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies: evidence of gene-environment interactions with heavy cigarette smokingArthritis Research & Therapy, 2008
- Interaction between smoking, the shared epitope, and anti–cyclic citrullinated peptide: A mixed picture in three large North American rheumatoid arthritis cohortsArthritis & Rheumatism, 2007
- Progression of radiographic joint damage in different eras: trends towards milder disease in rheumatoid arthritis are attributable to improved treatmentAnnals Of The Rheumatic Diseases, 2006
- Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian womenAnnals Of The Rheumatic Diseases, 2006
- A new model for an etiology of rheumatoid arthritis: Smoking may trigger HLA–DR (shared epitope)–restricted immune reactions to autoantigens modified by citrullinationArthritis & Rheumatism, 2005
- Calculating measures of biological interactionEuropean Journal of Epidemiology, 2005
- Screening the genome for rheumatoid arthritis susceptibility genes: A replication study and combined analysis of 512 multicase familiesArthritis & Rheumatism, 2003
- The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritisArthritis & Rheumatism, 1988
- The shared epitope hypothesis. an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritisArthritis & Rheumatism, 1987