arthritis. Of the 448 controls where data were available, 54% were female and the median age at the time of sample donation was 66 (interquartile range (IQR) 42–75). This data has been published previously.7 All cases and controls were of UK white Caucasian ethnicity. Genotyping Genotype frequencies for one SNP (ss38346943) deviated from Hardy–Weinberg equilibrium (p,0.01) in the control popula- tion and it was excluded from the susceptibility analysis. One variant (ss38346944) was not tested in the control samples, and hence investigation of this marker was restricted to the analysis of clinical outcome. Association with IP susceptibility Genotype distributions differed significantly at the PTPN22*C1858T polymorphism between IP cases and controls (p = 0.02) (table 2). In addition, there was a significant association between carriage of the PTPN22*1858T allele and IP (odds ratio (OR) = 1.42 (95% CI 1.06–1.90), p = 0.02). The strength of the effect was similar in the RA subgroup (OR = 1.38 (95% CI 1.01–1.89), p = 0.04) and the IP cohort as a whole. No association between IP and any of the other SNPs was detected either when analysed by genotype (table 2) or by allele. Stratifying the cohort for the fulfilment of ACR criteria for RA by 5 years did not alter these conclusions (data not shown). When the analysis was performed using logistic regression to adjust for the genotype at the rs2476601 (R620W) SNP, another SNP showed evidence for association with susceptibility: rs1217388 (SNP 32; uncorrected p = 0.003). However, the only haplotype occurring significantly more frequently in cases than controls was the haplotype carrying the risk allele at rs2476601 (R620W) (12.4% cases, 9.3% controls, p = 0.03). When chromo- somes carrying the risk allele were excluded, no evidence for association of the remaining haplotypes with RA was found. Furthermore, haplotypes carrying the risk allele at rs1217388 (SNP 32), showed no difference in frequency between cases and controls. Association with clinical outcome measures No association was detected for any of the SNPs tested, including the PTPN22*C1858T polymorphism, with either Table 1 Clinical data for subjects with inflammatory polyarthritis (IP) Characteristic RF positive, n (%): Baseline Erosive, n (%): By 1 year By 5 years Anti-CCP positive at baseline, n (%) ACR criteria fulfilled by 5 years, n (%) Median swollen joint count (IQR): At baseline At 5 years Median HAQ score (IQR): At baseline At 5 years Median CRP at baseline (IQR) Cases (n = 843) 202/773 (26%) 159/476 (33%) 202/487 (41%) 181/682 (27%) 519/769 (67%) 4 (1–10) 0 (0–1) 0.75 (0.25–1.38) 0.25 (0.25–1.5) 5 (0–15) The denominator details the number of subjects where information was available. ACR, American College of Rheumatology; CCP, cyclic citrinulated peptide; HAQ, Health Assessment Questionnaire; IQR, interquartile range; RF, rheumatoid factor. Ann Rheum Dis 2008;67:251–255. doi:10.1136/ard.2007.071894 Extended report erosive status or Larsen score by 5 years (table 3). A trend for association of the Larsen score by 5 years was noted with SNP rs1217413 (SNP35) but this was not significant when a Bonferroni correction was applied. Furthermore, no association with Larsen score at 1 year or with any other clinical outcome measure was detected (data not shown). None of the other SNPs tested demonstrated statistical evidence for association either in the IP cohort as a whole (table 3) or in the subgroup satisfying ACR criteria for RA by 5 years (data not shown). No association was detected with other markers of outcome tested such as HAQ score at presentation or by 5 years, swollen and tender joint counts at presentation or by 5 years or CRP at baseline for any of the SNPs spanning the gene (data not shown). Association with autoantibody status There was a significant association between the variant allele of the PTPN22*C1858T (rs2476601) SNP and baseline anti-CCP status in the RA subgroup (p = 0.003) (table 4). DISCUSSION In this unselected primary care-based inception cohort of patients, we have confirmed the association between the PTPN22*C1858T polymorphism and susceptibility to IP but found no association with severity using a number of clinical outcome markers. We have also failed to find any association between disease susceptibility or severity and other polymorph- isms spanning the gene. The association of the PTPN22*1858T variant with suscept- ibility to RA has been widely replicated in white European populations.4 This polymorphism has also been found to be associated with susceptibility in two other inception cohorts with early disease (OR 1.3 and 1.5).11 19 The effect size detected in the current study (OR = 1.4) is in keeping with those reports and suggests that the variant confers a modest increase in risk. One explanation for the lower effect sizes detected in studies of early disease compared to established series of RA patients may be that the PTPN22*C1858T variant is associated with disease severity as well as susceptibility. An inception cohort, such as NOAR, followed prospectively is required to dissect these issues. The NOAR cohort is representative of patients with new-onset IP seen in general practice. A total of 79.4% were referred to hospital within the 5 years of follow-up, while 75% satisfied ACR classification criteria for RA by 5 years. The choice of relevant outcome measures is the subject of some debate. The development of radiological erosions is generally regarded as a reliable and validated measure of severity but, the earlier use of disease-modifying (DMARD) therapy may mean that erosions are of less clinical relevance. Furthermore, the level of disability experienced by patients is of far greater impor- tance to them than x ray appearances. Hence, a measure of physical function such as the HAQ score may provide a more relevant outcome measure. We have tested multiple measures of disease outcome but, despite this, we have found no asso- ciation of the PTPN22*C1858T polymorphism with disease severity. One possibility is that the PTPN22*C1858T poly- morphism is associated with outcome but this was masked by the effect of treatment. This could occur if patients carry- ing the variant allele were more likely to receive DMARD treatment. However, this was not found to be the case (OR receiving DMARDs compared with not receiving DMARDs if carrying the PTPN221858*T variant = 1.36 (95% CI 0.84–2.24), p = 0.19). 253