Clinical relevance of Thiopurine methyl transferase genotype testing for azathioprine in dermatology.

Abstract

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

Methods: We included consecutive patients on Azathioprine who were initiated for dermatological disorders from south India. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) were assessed. A comparison of the proportion of adverse events to azathioprine, especially myelosuppression, was performed between those with wild-type genotype and those with TPMT polymorphisms.

Results: Of the 123 patients (61 males, mean age 46 years), 65% had autoimmune blistering disorder. Adverse event to azathioprine was noted in 25 (20.3%), of which 16 (13%) had myelosuppression, four (3.2%) each had hepatotoxicity and gastrointestinal intolerance. TPMT polymorphisms were detected amongst 13 (10.7%), of which five had experienced adverse events. The polymorphisms could explain 25% (4 out of 16) of the cases of leucopenia. The odds of developing leukopenia in TPMT polymorphism was not significant (3.63, 95% CI 0.96-13.60, p=0.055).

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