Extended report Table 2 controls rs1217414 (SNP 1) rs2488458 (SNP 2) rs12760457 (SNP 18) rs11102685 (SNP 20) rs12730735(SNP 21) rs2476601(SNP22) (PTPN22*C1858T) rs1310182 (SNP 27) rs1217388 (SNP 32) ss38346942 (SNP 34) rs1217413 (SNP 35) rs3811021 (SNP 36) Cases 736 746 731 742 736 832 683 736 720 732 699 Genotype data for single nucleotide polymorphisms (SNPs) spanning the PTPN22 gene in patients with inflammatory polyarthritis (IP) and SNP (no. from Carlton study) Sample size 1/1 n (%) 2/2 n (%) Sample size 1/1 n (%) 2/2 n (%) p Value (uncorrected) 386 (52.4) 425 (57.0) 355 (48.6) 614 (82.7) 360 (48.9) 641 (77.0) 227 (33.2) 416 (56.5) 694 (96.4) 433 (59.2) 446 (63.8) 1/2 n (%) 305 (41.4) 278 (37.3) 320 (43.8) 119 (16.0) 322 (43.8) 178 (21.4) 323 (47.3) 275 (37.4) 26 (3.6) 259 (35.4) 215 (30.8) 45 (6.1) 43 (5.8) 56 (7.7) 9 (1.2) 54 (7.3) 13 (1.6) 133 (19.5) 45 (6.1) 0 (0.0) 40 (5.5) 38 (5.4) Controls 398 387 390 403 357 412 351 400 386 383 386 221 (55.6) 209 (54.0) 182 (46.7) 340 (84.4) 169 (47.3) 342 (83.0) 101 (28.8) 208 (52.0) 375 (97.2) 240 (62.7) 247 (64.0) 1/2 n (%) 161 (40.4) 156 (40.3) 179 (45.9) 61 (15.1) 160 (44.8) 66 (16.0) 175 (49.9) 168 (42.0) 11 (2.8) 126 (32.9) 129 (33.4) 16 (4.0) 22 (5.7) 29 (7.4) 2 (0.5) 28 (7.9) 4 (1.0) 75 (21.3) 24 (6.0) 0 (0.0) 17 (4.4) 10 (2.6) 0.16 0.45 0.67 0.35 0.61 0.02 0.17 0.24 0.50 0.22 0.41 1, major (wild-type) allele; 2, minor (variant) allele. Recently, Carlton et al reported that three SNPs (rs1310182 (SNP 27), rs3811021 (SNP 36) and rs3789604 (SNP 37)) were associated with susceptibility to RA independently of the PTPN22*C1858T polymorphism.6 Their association with IP has not previously been determined. We did not test rs3789604 (SNP 37) in the current study but another SNP (rs3811021 (SNP 36)), which shows strong correlation with rs3789604, was examined. However, we found no association with suscept- ibility, either in IP as a whole or in the subgroup with RA, for any of the variants tested other than the PTPN22*C1858T polymorphism. Similarly, no evidence for association with severity measures was found, although it should be noted that the low minor allele frequencies for some of the SNP markers (particularly for ss38346944 (SNP 23), ss38346943 (SNP 28) and ss38346942 (SNP 34)) meant that power to test such association was limited. Although the PTPN22*C1858T polymorphism was not associated with clinical markers of severity, in the subgroup of patients who fulfilled the ACR classification criteria for RA by 5 years, a statistically significant association with the presence of anti-CCP antibodies at baseline was detected, in keeping with previous reports.11 20 The presence of anti-CCP antibodies is strongly associated with adverse outcome. For example, the odds ratio for the presence of erosions by 2 years in patients who are anti-CCP antibody positive at baseline has been reported as 5.4 (95% CI 1.7–17.0).21 Hence, although the PTPN22*1858T variant is associated with the presence of anti- CCP antibody, it is the autoantibody that appears to determine severity. The findings are in keeping with the hypothesis that the PTPN22*1858T allele, like HLA-DRB1 shared epitope alleles, may create a permissive environment for the production of these antibodies.22 In summary, carriage of the PTPN22*1858T variant allele is associated with susceptibility both to IP and RA, conferring a modest increase in risk of approximately 40%. The association appears to be solely accounted for by this SNP. Although the PTPN22*1858T variant allele was associated with the presence of anti-CCP autoantibodies, neither this nor other polymorph- isms spanning the gene were found to be clinically useful predictors of adverse outcome. Acknowledgements: We thank the Arthritis Research Campaign for their support. Funding: ARC grant reference no. 17552. Competing interests: None declared Table 3 Allelic association of single nucleotide polymorphisms (SNPs) spanning PTPN22 gene with erosive status and Larsen score by 5 years Erosive status by 5 years/minor allele frequency, n (%) Median Larsen* score at 5 years, by allele{ (IQR) Non-erosive, n Erosive, n (%) (%) SNP (no. from Carlton study) 86 (26.9) Rs1217414 (SNP 1) 73 (22.3) rs2488458 (SNP 2) 98 (30.4) rs12760457 (SNP 18) 34 (10.3) rs11102685 (SNP 20) 95 (29.5) rs12730735 (SNP 21) rs2476601 (SNP 22) (PTPN22*C1858T) 45 (11.1) ss38346944 (SNP 23) 9 (3.0) rs1310182 (SNP 27) 133 (43.2) ss38346943 (SNP 28) 15 (4.7) rs1217388 (SNP 32) 72 (22.2) ss38346942 (SNP 34) 3 (1.0) rs1217413 (SNP 35) 64 (19.6) rs3811021 (SNP 36) 68 (22.2) 114 (24.4) 119 (24.9) 150 (31.8) 40 (8.4) 147 (31.1) 65 (11.6) 8 (1.9) 180 (44.6) 19 (4.2) 118 (24.8) 10 (2.1) 114 (24.5) 99 (21.9) OR (95% CI) 1.14 (0.8–1.6) 0.86 (0.6–1.2) 0.94 (0.7–1.3) 1.30 (0.8–2.0) 0.92 (0.7–1.3) 0.96 (0.6–1.4) 1.62 (0.6–4.1) 0.95 (0.7–1.3) 1.13 (0.6–2.2) 0.87 (0.6–1.2) 0.43 (0.1–1.5) 0.75 (0.5–1.0) 1.0 (0.7–1.4) p Value 0.43 0.39 0.69 0.34 0.62 0.84 0.32 0.72 0.72 0.40 0.19 0.11 0.92 Allele 1 5 (0–20) 5 (0–21) 4 (0–21) 5 (0–20) 4 (0–21) 5 (0–20) 5 (0–20) 6 (0–23.5) 5 (0–21) 5 (0–21) 5 (0–20) 5 (0–22) 5 (0–20) Allele 2 6 (0–29) 4 (0–20) 5 (0–19) 9 (0–30) 5 (0–19) 5 (0–17) 10 (2–30) 5 (0–22) 6 (2–20) 4 (0–18) 0 (0–7) 3 (0–17) 3 (0–20) p Value{ 0.72 0.05 0.52 0.84 0.63 0.74 0.32 0.93 0.26 0.11 0.06 0.007 0.49 Uncorrected p values are presented. Allele 1, major (wild-type) allele; allele 2, minor (variant) allele. *Larsen score in all subjects with information available. When the analysis was restricted to patients who were erosive, the conclusions were not altered; {x2; {logistic regression by genotype. IQR, interquartile range; OR, odds ratio. 254 Ann Rheum Dis 2008;67:251–255. doi:10.1136/ard.2007.071894