Clinical relevance of thiopurine methyltransferase genotype testing for azathioprine in dermatology

Polymorphisms in thiopurine methyltransferase (TPMT) are a predominant cause of azathioprine-induced leucopenia in Western countries. The exact role of these polymorphisms in the Indian population with dermatological disorders is uncertain.

To evaluate the frequency of genetic polymorphism of TPMT and its impact on the safety of azathioprine in dermatological disorders.

We included consecutive patients on azathioprine who were initiated for dermatological disorders from South India. Three TPMT polymorphisms (c.238G>C, c.460G>A and c.719A>G) were assessed. The proportions of adverse events to azathioprine, especially myelosuppression, were compared between those with the wildtype genotype and those with TPMT polymorphisms.

Of the 123 patients (61 male and 62 female, mean age 46 years), 65% had an autoimmune blistering disorder. Adverse events to azathioprine were noted in 25 (20.3%), of whom 16 (13.0%) had myelosuppression and 4 (3.2%) each had hepatotoxicity and gastrointestinal intolerance. TPMT polymorphisms were detected in 13 (10.6%), of whom 5 had experienced adverse events. The polymorphisms could explain 25% (4 of 16) of the cases of leucopenia. The odds of developing leucopenia in patients with TPMT polymorphism were not significant (odds ratio 3.63, 95% confidence interval 0.96-13.6; P = 0.06).

The tested TPMT polymorphisms could not predict the adverse events of azathioprine, particularly the haematological toxicity, in dermatological use among the South Indian population.