Synergistic effect of having HLA–DRB1 *04:05 and *09:01 alleles in RA according to anticyclic citrullinated peptide autoantibodies (anti-CCP) status.
| RA | Anti-CCP-positive RA | Anti-CCP-negative RA | ||||
|---|---|---|---|---|---|---|
| Genotype | No. Cases/Controls | OR † (95% CI) | No. Cases/Controls | OR† (95% CI) | No. Cases/Controls | OR† (95% CI) |
| Non-risk/non-risk | 344/574 | reference | 220/574 | reference | 71/574 | reference |
| *09:01/non-risk | 251/151 | 2.72 (2.12–3.47) | 173/151 | 2.94 (2.24–3.87) | 31/151 | 1.63 (1.03–2.59) |
| *04:05/non-risk | 465/135 | 6.08 (4.79–7.72) | 359/135 | 7.54 (5.82–9.77) | 51/135 | 3.11 (2.07–4.67) |
| *09:01/*09:01 | 41/11 | 6.36 (3.20–12.63) | 29/11 | 6.92 (3.36–14.24) | 2/11 | 1.44 (0.31–6.64)# |
| *04:05/*04:05 | 76/9 | 15.22 (7.48–30.94) | 61/9 | 20.22 (9.77–41.82) | 2/9 | 1.85 (0.39–8.74)# |
| *04:05/*09:01 | 127/10 | 24.09 (12.41–46.79) | 90/10 | 28.03 (14.17–55.45) | 16/10 | 13.66 (5.93–31.44) |
| AP†† | 0.68 (0.46–0.89) | 0.66 (0.43–0.89) | 0.73 (0.49–0.96) | |||
| RERI†† | 16.38 (0.48–32.27) | 18.69 (–0.28–37.66) | 9.98 (–1.23–21.20) | |||
| S†† | 3.40 (1.68–6.88) | 3.19 (1.57–6.52) | 4.63 (1.75–12.26) | |||
| Multiplicity†† | p = 0.012 | p = 0.025 | p = 4.32 × 10−4 | |||
↵† 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)] and were adjusted for age and sex. Non-risk alleles indicates the absence of risk alleles, SE, and *09:01.
↵†† The attributable proportions (AP), relative excess risk due to interaction (RERI), synergy index (S) and multiplicity were calculated for interaction between *04:05 and *09:01 allele.
↵# These values were not statistically significant (p > 0.05). RA: rheumatoid arthritis.