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Azathioprine and its metabolite 6-mercaptopurine (6-MP) are widely used in the treatment of Crohn’s disease, ulcerative colitis, autoimmune hepatitis, and a range of other inflammatory and autoimmune diseases, as well as for prevention of transplant rejection. Thiopurine methyltransferase (TPMT) converts 6-MP to 6-methylMP.1,2 Deficiency of its expression predisposes treated patients to bone marrow depression; it may also enhance the efficacy of thiopurines by increasing their metabolism to 6-thioguanine nucleotides.1,2 Previous reports in Caucasians have shown that approximately 0.3% are homozygously and 10% heterozygously deficient in TPMT.1,2 One study suggests that the frequency of individuals with the mutant TPMT allele, TPMT*3A, is lower in Southwest Asians than in Caucasians3; this variant allele causes reduced enzyme activity in vitro.3 However, there are no data on the phenotypic expression of TPMT in South Asian populations.
We have compared expression of TPMT in South Asian and Caucasian patients attending gastroenterology, renal, rheumatology, and dermatology clinics who were being considered for treatment with thiopurines. TPMT activity was assayed by tandem mass spectrometry for 6-methylMP (assays kindly provided by Purine Research Laboratory, Guy’s Hospital, London SE1 9RT, UK). Homozygous deficiency of TPMT was defined as a level <10, heterozygous as 10–25, and normal as > 25 pmol/h/mg haemoglobin.
Of 83 Caucasian patients, one (1.3%) was homozygously deficient, 10 (12%) were heterozygous, and 72 (86.7%) had normal expression of TPMT. The corresponding values in 77 South Asian patients were 0, 7 (9%), and 70 (91%), respectively.
The prevalence of deficiency of expression of TPMT in South Asian patients resembles that in Caucasians. Use and monitoring of azathioprine and 6-MP should therefore follow similar principles in both ethnic groups.
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