Pharmacogenetic Effect of Thiopurine Methyl Transferase (TPMT) Gene Expression and Serum TNF on the Imuran Response in Ulcerative Colitis (UC) Iraqi Patients

Background: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), exerts its impact on both rectal and colonic mucosa, with a growing incidence. This study aims to explore the pharmacogenetic influence of thiopurine methyl transferase (TPMT) gene expression and serum tumor necrosis factor (TNF) levels on the response to Imuran in Iraqi patients with UC. Methods: Seventy individuals with chronic UC and ۳۰ healthy controls were enrolled in this investigation. RNA extraction using the triazole method and enzyme-linked immunosorbent assay (ELISA) for TNF measurement were employed. Patients, aged ۱۵-۵۰ years, underwent Imuran treatment. Results: Diverse responses to Imuran were observed among patients, with TPMT gene expression levels below ۱ in ۳۵ patients leading to side effects, while the remaining ۳۵ patients exhibited positive responses with TPMT gene expression exceeding ۱. Patients with varying degrees of severe, moderate, and mild UC associated with TNF showed a significant correlation with Imuran non-response. Conclusions: A distinct correlation was identified between TPMT gene expression and Imuran therapy outcomes in UC patients. Further investigation is warranted to elucidate the underlying mechanism, positioning the TPMT gene as a potential therapeutic target for mitigating the impact of UC.