Risk of having anticyclic citrullinated peptide autoantibody (anti-CCP)-positive and anti-CCP-negative RA according to HLA–DRB1 and smoking status.
| Anti-CCP-positive RA | Anti-CCP-negative | |||
|---|---|---|---|---|
| HLA-DRB1/Smoking | No. Cases/Controls | OR† (95% CI) | No. Cases/Controls | OR† (95% CI) |
| SE | ||||
| −/− | 188/502 | reference | 58/502 | reference |
| −/+ | 30/63 | 2.17 (1.25–3.77) | 13/63 | 3.76 (1.74–8.15) |
| +/− | 826/328 | 7.28 (5.85–9.06) | 99/328 | 2.66 (1.87–3.79) |
| +/+ | 166/46 | 16.31 (9.96–26.74) | 22/46 | 9.05 (4.43–20.37) |
| AP†† | 0.48 (0.25–0.71) | 0.43 (0.02–0.81) | ||
| RERI†† | 7.87 (0.53–15.21) | 4.08 (–2.34–10.50) | ||
| S†† | 2.06 (1.28–3.31) | 1.92 (0.84–4.41) | ||
| HLA–DRB1 *01:01 | ||||
| −/− | 188/502 | reference | 58/502 | reference |
| −/+ | 30/63 | 2.67 (1.43–4.97) | 13/63 | 3.34 (1.43–7.78) |
| +/− | 200/124 | 4.54 (3.39–6.08) | 26/124 | 1.87 (1.15–3.22) |
| +/+ | 42/17 | 12.02 (5.69–25.39) | 5/17 | 4.92 (1.43–16.91) |
| AP†† | 0.48 (0.12–0.84) | 0.14 (−0.88–1.17)# | ||
| RERI†† | 5.81 (−2.56–14.17) | 0.71 (−5.07–6.50) | ||
| S†† | 2.11 (0.99–4.54) | 1.22 (0.27–5.62) | ||
| HLA–DRB1*04:05 | ||||
| −/− | 188/502 | reference | 58/502 | reference |
| −/+ | 30/63 | 2.06 (1.15–3.67) | 13/63 | 3.40 (1.53–7.57) |
| +/− | 516/142 | 11.18 (8.60–14.54) | 58/142 | 3.68 (2.44–5.57) |
| +/+ | 97/22 | 19.50 (10.43–36.45) | 13/22 | 9.95 (4.03–24.54) |
| AP†† | 0.37 (0.01–0.74) | 0.38 (−0.13–0.90)# | ||
| RERI†† | 7.26 (−4.24–18.75) | 3.86 (−4.30–12.03) | ||
| S†† | 1.65 (0.88–3.07) | 1.76 (0.68–4.53) | ||
| HLA–DRB1*10:01 | ||||
| −/− | 188/502 | reference | 58/502 | reference |
| −/+ | 30/63 | 2.33 (1.20–4.50) | 13/63 | 3.24 (1.34–7.87) |
| +/− | 97/34 | 7.60 (4.91–11.76) | 7/34 | 1.69 (0.72–4.01)# |
| +/+ | 22/3 | 36.39 (9.29–142.61) | 2/3 | 13.06 (1.75–98.67)# |
| AP†† | 0.76 (0.42–1.08) | 0.70 (0.12–1.28) | ||
| RERI†† | 27.46 (−21.69–76.62) | 9.22 (−16.55–34.99) | ||
| S†† | 4.46 (1.10–18.08) | 4.14 (0.48–35.65) | ||
| HLA–DRB1*09:01 | ||||
| −/− | 188/502 | reference | 58/502 | reference |
| −/+ | 30/63 | 2.54 (1.41–4.60) | 13/63 | 2.90 (1.30–6.45) |
| +/− | 292/162 | 4.97 (3.83–6.44) | 41/162 | 2.19 (1.41–3.40) |
| +/+ | 47/33 | 7.77 (4.12–14.63) | 13/33 | 5.66 (2.38–13.45) |
| AP†† | 0.16 (−0.32–0.65)# | 0.28 (−0.32–0.87)# | ||
| RERI†† | 1.25 (−3.21–5.72) | 1.57 (−2.85–0.87) | ||
| S†† | 1.23 (0.63–2.38) | 1.51 (0.54–4.20) | ||
↵† OR were calculated by comparing each group with the corresponding reference group [individuals without HLA–DRB1 risk alleles (*01:01, *04:01, *04:04, *04:05, *04:08, *04:10, *09:01, *10:01)], adjusted for age and sex. HLA–DRB1 shared epitope (SE) indicates *01:01, *04:01, *04:04, *04:05, *04:08, *04:10, and *10:01. Subjects with no available smoking history or the rare alleles (*0102, *1402, and *1406) were excluded from the analysis.
↵†† The attributable proportions (AP), relative excess risk due to interaction (RERI), and synergy index (S) were calculated for gene-environmental interaction.
↵# Not statistically significant (p > 0.05). RA: rheumatoid arthritis.