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Thiopurine methyltransferase activity in American white subjects and black subjects
Author(s) -
McLeod Howard L,
Lin JinSying,
Scott Edward P,
Pui ChingHon,
Evans William E
Publication year - 1994
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1994.4
Subject(s) - thiopurine methyltransferase , mercaptopurine , population , pharmacology , methyltransferase , chemistry , medicine , biochemistry , methylation , azathioprine , disease , environmental health , gene
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 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. Clinical Pharmacology and Therapeutics (1994) 55, 15–20; doi: 10.1038/clpt.1994.4