Evaluation of genetic variants associated with the risk of thiopurine-related pancreatitis: a case control study from ENEIDA registry.

BACKGROUND: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. AIM: Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled, 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis, and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Prevalence, incidence and mortality of inflammatory bowel disease in Catalonia. A population-based analysis.

INTRODUCTION: Few recent data on the epidemiology of inflammatory bowel disease (IBD) are available, especially in Southern Europe. AIM: To evaluate the prevalence, incidence and mortality of IBD in Catalonia during the period 2011-2016. MATERIAL AND METHODS: Data on the prevalence, incidence and mortality of IBD were obtained from the Catalan Health Surveillance System (CHSS). Crude incidence and prevalence rates were calculated for all the Catalan population. Trends in age-sex-adjusted rates were also estimated, and logistic regression was used to calculate the adjusted mortality odds ratio (OR). Data for Crohn's disease (CD) and ulcerative colitis (UC) were analyzed separately. RESULTS: The prevalence per 100,000 inhabitants in 2016 was 353.9 for UC and 191.4 for CD. The total number of IBD patients rose from 29543 in 2011 to 40614 in 2016. IBD was associated with significantly elevated adjusted mortality ratios: 1.28 (95% CI: 1.6-1.4) for UC and 1.85 (95% CI: 1.62-2.12) for CD. CONCLUSIONS: IBD prevalence is very high and is increasing rapidly in Catalonia. Both CD and UC are associated with significantly higher mortality rates. Key message Crohn disease and ulcerative colitis present a small but significant increase in mortality compared to non-inflammatory bowel disease. The prevalence of inflammatory bowel disease is increasing rapidly in Catalonia. Data on prevalence and incidence suggest that the number of patients may double in approximately 10 years.