rs2476601 polymorphism in PTPN22 is associated with Crohn's disease but not with ulcerative colitis: a meta-analysis of 16,838 cases and 13,356 controls

Authors Abdellah Hedjoudje, Chérifa Cheurfa, Clément Briquez, Allen Zhang, Stéphane Koch, Lucine Vuitton.


Background Although the rs2476601 polymorphism of PTPN22 has been reported to be a susceptibility gene for Crohn's disease (CD), results from different studies vary and remain inconclusive. Also, no association has been found between rs2476601 and the risk of ulcerative colitis (UC). The aim of this meta-analysis was to investigate the association between this PTPN22 polymorphism (rs2476601) and the risk of inflammatory bowel disease, UC and CD.

Methods We performed a meta-analysis by identifying relevant candidate gene-based studies from EMBASE and MEDLINE. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the strength of associations between rs2476601 and inflammatory bowel diseases, using a fixed effect or random effect model. Publication bias was also assessed.

Results By pooling 14 different studies, 13,356 controls, 8182 patients with CD, and 8656 with UC were included. We found that the T allele of PTPN22 was not significantly associated with a higher risk of developing UC (OR 1.06, 95%CI 0.98-1.14) but was associated with a decreased risk of developing CD (OR 1.28, 95%CI 1.17-1.40). The T allele in rs2476601 lowered the risk of CD by 22%.

Conclusion This study shows that PTPN22 (rs2476601) is significantly associated with the risk of developing CD, but has no association with UC. This suggests that these diseases have different pathways involved in their pathophysiology.

Keywords Meta-analysis, candidate gene study, PTPN22, inflammatory bowel disease, polymorphism

Ann Gastroenterol 2017; 30 (2): 197-208

Original Articles