Interaction of HLA-DRB1 shared epitope and smoking on the development of anti-citrullinated protein antibody positive rheumatoid arthritis in Greek patients
Authors' conclusion
We identified that smoking and the presence of SE alleles increased the risk of developing ACPA-positive RA, indicating a strong genetic-environmental correlation that probably triggers the pathogenesis of RA in Greek patients.
Study context
- Population
- Greek patients with longstanding rheumatoid arthritis (RA), smokers and non-smokers, and Greek controls
- Participants
- 300 vs 346
- Comparison
- Greek patients with RA vs Greek controls
- RAn = 300
- Controlsn = 346reference
- Outcome
- Interaction of HLA-DRB1 SE alleles and smoking on ACPA-positive RA
Main finding
As reported in the abstract
Odds ratio (CI)P value
Single SE carriers in combination with smoking
6.53(1.47–28.91)
P = 0.013Smokers with a double gene copy
15.27(1.39–167.52)
P = 0.026HLA-DRB1 *01:01 SE allele (strongest interaction)
12.55(1.32–119.35)
P = 0.028Observational data: associations, not effects.
Further findings
RA development, any SE
| OR (CI) | P value | ||
|---|---|---|---|
| Any SE | 4.37 (3.13–6.11) | P < 0.001 | |
| 0.10.31310Odds ratio (log scale) |
ACPA production, any SE allele
| OR (CI) | P value | ||
|---|---|---|---|
| Any SE allele | 4.3 (2.57–7.22) | P < 0.001 | |
| 0.10.31310Odds ratio (log scale) |
ACPA-negative RA, SE genes combined with smoking
| OR (CI) | P value | ||
|---|---|---|---|
| SE genes and smoking | 2.01 (0.76–5.26) | P = 0.15 | |
| 0.20.5125Odds ratio (log scale) |
HLA-DRB1 alleles, RA vs controls
- Increased frequency of HLA-DRB1 *01:01, *10:01, *04:04 and *04:05 alleles in Greek patients
- Protective role of *04:03 allele
Original publication
Interaction of HLA-DRB1 shared epitope and smoking on the development of anti-citrullinated protein antibody positive rheumatoid arthritis in Greek patients. Clin Exp Rheumatol. Published 31 March 2025. doi:10.
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