TPMT Genotyping in 1000 Indian Patients: 14-Year Experience from a Tertiary-Care Hospital

Thiopurine methyltransferase (TPMT) enzyme plays a key role in the metabolism of the thiopurine drugs that are used for the treatment of inflammatory diseases. Mutations in the TPMT gene cause abnormal metabolism, resulting in toxicity; therefore, TPMT genetic analysis has been recommended for effective dose management. We retrospectively analysed data to determine the distribution of TPMT genotypes in a western Indian population. TPMT genotyping test was performed on 1000 patients with different inflammatory conditions between January 2009 and October 2023. The common TPMT genotypes *2, *3A, *3B and *3C were detected by amplification refractory mutation system - polymerase chain reaction (ARMS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. TPMT mutants were detected in 36 (3.6%) patients, of whom 14 (39%) had TPMT*1/*3A, 19 (53%) had TPMT*1/*3C, two (5.5%) had TPMT*1/*3B, and one (2.8%) had TPMT*3B/*3B alleles; mutant allele frequencies were 0.7% for *3A, 0.2% for *3B and 1.65% for *3C. A sub-group analysis explained thiopurine toxicity in only 33% patients by TPMT gene polymorphism whereas in 67% the toxicity remained unexplained. The low prevalence of TPMT mutants (3.6%) along with unexplained thiopurine toxicity suggest that TPMT genotyping solely might be clinically less relevant in patients of Indian origin, underscoring the role of other genetic factors that may be involved in thiopurine toxicity in these patients.