THIOPURINE METHYLTRANSFERASE ACTIVITY IN AMERICAN WHITE SUBJECTS AND BLACK SUBJECTS

Background: Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulthydryl compounds, including 6-mercaptopurine. TPMT exhibits genetic polymorphism in white populations, with 89% of individuals having high TPMT activity, 11% having intermediate activity, and one in 300 having extremely low or absent activity. TPMT activity is inversely correlated with formation of active 6-mercaptopurine metabolites (thioguanine nucleotides), thereby influencing 6-mercaptopurine toxicity and efficacy. Methods: To investigate ethnic and gender differences in TPMT, we measured erythrocyte TPMT activity in 209 white healthy subjects and 196 black healthy subjects (202 women and 203 men). Results: The black population had lower TPMT activity than the white population (median, 14.4 versus 16.8 units/ml packed erythrocytes; p < 0.001). Maximum likelihood estimation of TPMT activity distribution identified 91.9% and 93.9% with high activity and 7.7% and 6.1% with intermediate activity in the white and black groups, respectively. Conclusions: These data indicate that TPMT activity is similarly polymorphic in American black subjects and white subjects, although median TPMT activity is approximately 17% lower in black subjects.