Clinical Pharmacogenetics Implementation... : Clinical Pharmacology & Therapeutics (original) (raw)

Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing

M V Relling
E E Gardner
W J Sandborn
K Schmiegelow
C-H Pui
S W Yee
C M Stein
M Carrillo
W E Evans
T E Klein

Clinical Pharmacology & Therapeutics

(

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387

391

March 2011

| DOI: 10.1038/clpt.2010.320

Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (˜1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30-60% of individuals who are heterozygotes (˜3-14% of the population) show moderate toxicity, and homozygous wildtype individuals (˜86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates athttp://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.