Thiopurine S-methyltransferase activity in Nigerians: phenotypes and activity reference values

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OBJECTIVES: This study assessed the activity of thiopurine S-methyltransferase (TPMT) in Nigerians with a view to providing data on susceptibility to thiopurine toxicity, and as well generate reference activity values for clinical use. RESULTS: TPMT activity, expressed as the amount of 6MMP in ng/mL after 1 h incubation at 37 °C per haemoglobin (U/g Hb), varied between 2.34 and 63.50 U/g Hb in the study population. Poor metabolic phenotypes, characterised by an activity values below 8.41 U/g Hb, were observed in 20% of the study subjects. Intermediate metabolizers had activity values between 8.41 and 16.13 U/g Hb. Fast and very fast metabolizers were characterised by activity values of 16.20-56.22 and > 56.22 U/g Hb, respectively. These findings suggest that a potentially huge discordance between TPMT phenotype and genotype exist in Nigerians, and emphasizes the superiority of a prior determination of TPMT metabolic phenotype in ensuring the safety of thiopurine drug administration in the population.

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