Abstract
therefore aimed to find genetic and clinical factors predictive of thiopurine induced AE in patients with CD. Methods: Four hundred and sixty eight CD patients were screened and one hundred and eighty one patients treated with thiopurines were included in our study. Thiopurine AE included were myelosuppression, hepatotoxicity and pancreatitis. Clinical data collected included age, ethnicity, gender and smoking status. Patients’ DNAwas tested for specific polymorphisms in the TPMT, GSTM1and GSTT1 genes. Results: Twenty-seven patients (15%) developed AE requiring thiopurine discontinuation. The most common AE was myelosuppression (12 patients), followed by pancreatitis (9 patients) and hepatotoxicity (6 patients). Univariate analysis showed that patients developing AE were significantly older when receiving thiopurines (mean 34.19±14.0 vs. 27.95±11.7 years old, P= 0.016) and more likely to be current or past smokers (51.9% vs 30.0%, P= 0.044). Specifically, patients who developed thiopurine induced pancreatitis were more likely to be past or present smokers (p = 0.001), and patients who developed hepatotoxicity were older than patients who did not develop AE (p = 0.014). Only four patients (2.2%) were heterozygous for TPMT polymorphisms, and none developed thiopurine induced AE. No association was found between GSTM1 or GSTT1 polymorphisms and the development of AE (p = 0.08 for GSTM1 wild-type). On multi-variant analysis past or current smokers were at increased risk for developing thiopurine related AE (OR 2.84, CI 95%: 1.104 7.296). Conclusions: TPMT, GSTM1 and GSTT1 genotype did not predict development of thiopurine induced AE in our patients. Past or current smokers were at increased risk for thiopurine induced AE, specifically pancreatitis. These findings may have implications for decision making in treating CD patients with thiopurines.
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