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Dr. Lal Krishna U.
Dr. Saji Sebastian
Dr. Ramu M.
Dr. Sandesh K
Dr Deni Joseph
Dr. Nithya V.
Dr. Gaurav Khatana
Dr. Gino Rony Philip


TPMT, NUDT, Inflammatory Bowel Disease, Azathioprine


Background: This study explores the prevalence of genetic polymorphisms in the TPMT and NUDT15 genes and their association with Azathioprine-induced leucopenia in South Asia, focusing on Kerala. Azathioprine, a commonly used immunosuppressive medication, is crucial in managing Inflammatory Bowel Disease (IBD) and Autoimmune Hepatitis. This research seeks to determine the impact of these polymorphisms and their potential role in individualized treatment strategies.

Methods: Conducted as a prospective observational study, the research involves patients diagnosed with IBD and Autoimmune Hepatitis. Genetic analysis is employed to estimate the prevalence of TPMT and NUDT15 genetic polymorphisms. The study underscores the necessity of genetic assessments to inform treatment decisions and improve safety by minimizing severe adverse reactions.

Results: we observed genetic variation in NUDT 15 genotyping, with allele frequencies predominantly showing the 1* allele (90.7%) and a heterozygous allele combination of 1*/3* (9.3%), evidenced by the c.415C> T:p,R139C variant. Additionally, all participants demonstrated the genetic polymorphism TPMT*1/*1 (wild-type), indicating normal enzymatic activity. The study provides insights into patient demographics, clinical history, symptoms, severity, and treatment modalities.

Discussion emphasizes the rising incidence of IBD and Autoimmune Hepatitis in South Asia, particularly India, and the cost-effective significance of Azathioprine in managing these conditions. Genetic variations, particularly in NUDT15 gene variants, are identified as predictors of Azathioprine-induced leucopenia. The study underscores the potential of NUDT15 genotyping for personalized dosing, aligning with recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines.

Conclusion: In conclusion, this research underscores the importance of understanding genetic variations to optimize Azathioprine therapy. By incorporating genetic insights, notably NUDT15 genotyping, clinicians can enhance treatment decisions, patient safety, and overall care quality. Routine CBC monitoring is recommended as a cost-effective strategy for Azathioprine treatment, enabling proactive management of adverse effects. This study contributes valuable insights for informed therapeutic strategies and improved treatment outcomes in the South Asian population.

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