Ethnic variation of thiopurineS-methyltransferase activity: a large, prospective population study

Abstract

The use of azathioprine (and its metabolite mercaptopurine) is limited by toxicity, especially myelosuppression, which is related to activity of the enzyme thiopurine S-methyltransferase (TPMT). TPMT activity varies between individuals and is considered deficient in one in 300 cases. We identified TPMT activity within an ethnically diverse population of patients attending an inner-city hospital phlebotomy service. A total of 1000 subjects were recruited and analyzed with respect to age, sex and ethnicity. Samples were analyzed from 456 Caucasians, 342 South Asians and 180 Afro-Caribbeans. Six subjects had deficient TPMT activity (0.6%: four women, two men; four Caucasians, one Afro-Caribbean, one South Asian). TPMT activity (nmol 6-methylthioguanine (6-MTG)/gHb/h) ranged 0-76 (median [interquartile range]: 33 [28-39]). Enzyme activity was lower in Afro-Caribbeans (30 [25-37.5]) than Caucasians (34 [29-40]) and South Asians (33 [29-38]), which was significant after adjustment for age and sex (p < 0.0001). Activity was lower in women (p = 0.022), especially South Asian females (n = 194; 32 [28-36]), compared with (35 [30-40]) in men (n = 148; p = 0.002). A higher prevalence of TPMT deficiency was recorded than in previous studies. Afro-Caribbeans have lower activity than Caucasians and South Asians. TPMT enzyme activity was lower among females, especially in South Asians.