Unwanted side effects from azathioprine medication can develop in those who have low thiopurine S-methyltransferase activity (AZA). The disorder affected around 11% of the European population and is caused by genetic variations in the TPMT gene. Around 0.3% of Europeans had defective TPMT variations, putting them at risk of suffering life-threatening bone marrow poisoning. For a study, researchers sought to quantify the incidence of TPMT gene mutations in Czech patients with rheumatic disorders and to examine the side effects of AZA medication in these individuals. Using PCR amplification and direct sequencing, 200 patients were tested for the existence of genetic allelic variations. They found genetic allelic variations altering TPMT activity in 19 individuals, one of whom had an unreported heterozygous mutation c.85T>C (p.W29R); 15 patients were moved from AZA to another medicine, and one patient was given a lower dose of AZA.

The relevance of checking for TPMT gene variations before using AZA in clinical rheumatology practice was demonstrated by the findings. Patients taking AZA who had experienced bouts of leukopenia or have had increased liver biochemical tests should have their TPMT genotype and/or enzyme activity tested.