BACKGROUND: Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl 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 303 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.
BACKGROUND:Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl 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-mercaptopurinetoxicity 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 303 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.
Authors: Tatyana V Nasedkina; Natalia A Guseva; Olga A Gra; Olga N Mityaeva; Alexander V Chudinov; Alexander S Zasedatelev Journal: Mol Diagn Ther Date: 2009 Impact factor: 4.074
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Authors: Gabriele Stocco; Wenjian Yang; Kristine R Crews; William E Thierfelder; Giuliana Decorti; Margherita Londero; Raffaella Franca; Marco Rabusin; Maria Grazia Valsecchi; Deqing Pei; Cheng Cheng; Steven W Paugh; Laura B Ramsey; Barthelemy Diouf; Joseph Robert McCorkle; Terreia S Jones; Ching-Hon Pui; Mary V Relling; William E Evans Journal: Hum Mol Genet Date: 2012-07-30 Impact factor: 6.150
Authors: H L Tai; E Y Krynetski; C R Yates; T Loennechen; M Y Fessing; N F Krynetskaia; W E Evans Journal: Am J Hum Genet Date: 1996-04 Impact factor: 11.025