TPMT gene variants in inflammatory bowel disease patients

Objective: Patients with Inflammatory Bowel Disease (IBD) frequently use thiopurine drugs for treatment, yet responses and side effects vary significantly. This study aims to investigate the prevalence of TPMT variants in IBD populations and their impact on thiopurine metabolism, treatment response, and adverse reactions. Materials and Methods: This clinical research employed a cross-sectional study design. The statistical population comprised individuals with inflammatory bowel disease (IBD). Participants were selected using a cross-sectional method to represent a diverse range of demographic and disease characteristics. They were stratified by disease severity and TPMT genotype. The study processes included genomic DNA isolation, sample preparation, DNA amplification, High-Resolution Melting Analysis (HRMA), data analysis and interpretation, statistical analysis, and final interpretation. Results: The most common TPMT genotype found in IBD patients was the wild type (TPMT1/1), accounting for 90% of cases. The TPMT2/2, TPMT1/2, TPMT1/3B, TPMT1/3A, and TPMT1/3C genotypes were less frequent, with prevalences of 3%, 4%, 1%, 1%, and 1%, respectively. Specifically, the TPMT2 genotype stands out with a high incidence of adverse events (leukopenia and pancreatitis) at 100%, underscoring the importance of genetic screening prior to treatment. Conclusion: This study reveals that different TPMT genotypes result in distinct biochemical and clinical outcomes in IBD patients. Specifically, the TPMT2, TPMT1/2, and TPMT3A genotypes are strongly associated with severe adverse events such as leukopenia and pancreatitis. The high incidence of TRAEs associated with these genotypes underscores the critical need for personalized treatment strategies. The TPMT2, TPMT3B, and TPMT3A genotypes exhibit different values in certain biochemical parameters, which may be attributed to their impact on the metabolism of these respective parameters. In conclusion, considering genetic factors in IBD treatment is essential for optimizing therapeutic responses and minimizing potential side effects. Keywords: TPMT, Gene Variants, Inflammatory Bowel Disease, Biochemical Markers, Adverse Events, Leukopenia, Pancreatitis