THIOPURINE METHYLTRANSFERASE ACTIVITY IN AMERICAN WHITE SUBJECTS AND BLACK SUBJECTS

Background: Thiopurine methyltransferase (TPMT) is a cytoplasmic enzym e that preferentially catalyzes the S-methylation of aromatic and hete rocyclic sulthydryl compounds, including 6-mercaptopurine. TPMT exhibi ts genetic polymorphism in white populations, with 89% of individuals having high TPMT activity, 11% having intermediate activity, and one i n 300 having extremely low or absent activity. TPMT activity is invers ely correlated with formation of active 6-mercaptopurine metabolites ( thioguanine nucleotides), thereby influencing 6-mercaptopurine toxicit y and efficacy. Methods: To investigate ethnic and gender differences in TPMT, we measured erythrocyte TPMT activity in 209 white healthy su bjects and 196 black healthy subjects (202 women and 203 men). Results : The black population had lower TPMT activity than the white populati on (median, 14.4 versus 16.8 units/ml packed erythrocytes; p < 0.001). Maximum likelihood estimation of TPMT activity distribution identifie d 91.9% and 93.9% with high activity and 7.7% and 6.1% with intermedia te activity in the white and black groups, respectively. Conclusions: These data indicate that TPMT activity is similarly polymorphic in Ame rican black subjects and white subjects, although median TPMT activity is approximately 17% lower in black subjects.