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P729 The clinical relevance of the CD-associated SNP within the gene locus encoding protein tyrosine phosphatase non-receptor type 22 in patients of the Swiss IBD Cohort

J. Zeitz*1, M. Spalinger1, L. Biedermann1, J.-B. Rossel2, M. C. Sulz1, 3, S. R. Vavricka1, 4, M. Fried1, 4, G. Rogler1, 4, M. Scharl1, 4

1University Hospital Zurich, Division of Gastroenterology and Hepatology, Zürich, Switzerland, 2Université de Lausanne, Institute of Social and Preventive Medicine, Lausanne, Switzerland, 3Kantonsspital St. Gallen, Division of Gastroenterology and Hepatology, St. Gallen, Switzerland, 4University of Zurich, Zurich Centre for Integrative Human Physiology, Zürich, Switzerland

Background

The single nucleotide polymorphism (SNP) rs2476601 within the PTPN22 gene results in altered PTPN22 protein function and is associated with increased risk for several autoimmune disorders (eg, rheumatoid arthritis, systemic lupus erythematosus, and type I diabetes) but reduces the risk for Crohn’s disease (CD). Experimental data demonstrated an important role for PTPN22 in immune cell function and intestinal homeostasis, but so far, it has not been addressed how the presence of SNP rs2476601 affects clinical characteristics in diseased patients. Here, we investigated associations of PTPN22 SNP rs2476601 and clinical characteristics of affected inflammatory bowel disease (IBD) patients in the Swiss IBD Cohort Study (SIBDCS).

Methods

In total, 2 066 IBD patients, consisting of 1 194 (57.8%) CD and 872 (42.2 %) ulcerative colitis (UC) patients from the SIBDCS were included. Epidemiologic, disease, and treatment characteristics were analysed for an association with the presence of the PTPN22 SNP rs2476601 isoforms ‘homozygous wild-type’ (GG), ‘heterozygous’ (GA), and ‘homozygous variant’ (AA).

Results

Of the entire set of patients, 13 patients (0.6%) had the AA genotype of the PTPN22 polymorphism, 275 (13.3%) carried the heterozygous (GA), and 1 778 (86.1%) the homozygous GG form. When comparing UC and CD patients, the presence of the A-allele (AA or GA genotype) was significantly lower in CD patients (p = 0.001). In CD, presence of the A-allele was associated with significantly less use of steroids and antibiotics (p = 0.022 and p = 0.037, respectively). In UC, presence of the A-allele was associated with less use of azathioprine and anti-TNF antibodies (p = 0.030 and p = 0.028, respectively). Whereas in CD, there was no association of the PTPN22 polymorphism with disease characteristics, in UC, statistically fewer patients with the PTPN22 polymorphism showed malabsorption syndrome (p = 0.023).

Conclusion

Our data suggest a protective role of the A-allele. This protection seems to be relevant not only for disease onset, as previously shown by GWAS, but also for disease development in affected patients, because A-allele carriers seem to develop less severe disease. Although GWAS did not reveal an association of SNP rs2476601 with UC, our findings suggest that it might have some protective role in affected UC patients. Taken together, our study for the first time addressed how the presence of SNP rs2476601 affects clinical characteristics in IBD patients.