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; Paul C. Stein; Maria Berrocal Carrillo; W E Evans; T E Klein; Clinical Pharmacogenetics Implementation Consortium

doi:http://dx.doi.org/10.1038/clpt.2010.320

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, Paul C. Stein, Maria Berrocal Carrillo, W E Evans, T E Klein, Clinical Pharmacogenetics Implementation Consortium

403 Citations (Scopus)

Abstract

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 wild-type individuals (~86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.

Original language	English
Journal	Clinical Pharmacology and Therapeutics
Volume	89
Issue number	3
Pages (from-to)	387-91
Number of pages	5
ISSN	0009-9236
DOIs	https://doi.org/10.1038/clpt.2010.320
Publication status	Published - Mar 2011

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Relling, M. V., Gardner, E. E., Sandborn, W. J., Schmiegelow, K., Pui, C-H., Yee, S. W., Stein, P. C., Carrillo, M. B., Evans, W. E., Klein, T. E., & Clinical Pharmacogenetics Implementation Consortium (2011). Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clinical Pharmacology and Therapeutics, 89(3), 387-91. https://doi.org/10.1038/clpt.2010.320

Relling, MV, Gardner, EE, Sandborn, WJ, Schmiegelow, K, Pui, C-H, Yee, SW, Stein, PC, Carrillo, MB, Evans, WE, Klein, TE & Clinical Pharmacogenetics Implementation Consortium 2011, 'Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing', Clinical Pharmacology and Therapeutics, vol. 89, no. 3, pp. 387-91. https://doi.org/10.1038/clpt.2010.320

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abstract = "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 wild-type individuals (~86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.",

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AU - Relling, M V

AU - Gardner, E E

AU - Sandborn, W J

AU - Schmiegelow, K

AU - Pui, C-H

AU - Yee, S W

AU - Stein, Paul C.

AU - Carrillo, Maria Berrocal

AU - Evans, W E

AU - Klein, T E

AU - Clinical Pharmacogenetics Implementation Consortium

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N2 - 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 wild-type individuals (~86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.

AB - 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 wild-type individuals (~86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.

U2 - http://dx.doi.org/10.1038/clpt.2010.320

DO - http://dx.doi.org/10.1038/clpt.2010.320

M3 - Journal article

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EP - 391

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

IS - 3

ER -

Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing

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