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: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

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496 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Clinical Pharmacology and Therapeutics
Vol/bind	89
Udgave nummer	3
Sider (fra-til)	387-91
Antal sider	5
ISSN	0009-9236
DOI	https://doi.org/10.1038/clpt.2010.320
Status	Udgivet - 2011

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10.1038/clpt.2010.320

Citationsformater

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, bind 89, nr. 3, s. 387-91. https://doi.org/10.1038/clpt.2010.320

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title = "Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing",

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.",

keywords = "6-Mercaptopurine, Antimetabolites, Antineoplastic, Azathioprine, Dose-Response Relationship, Drug, Genotype, Humans, Immunosuppressive Agents, Methyltransferases, Thioguanine",

author = "Relling, {M V} and Gardner, {E E} and Sandborn, {W J} and K Schmiegelow and C-H Pui and Yee, {S W} and Stein, {Paul C.} and Carrillo, {Maria Berrocal} and Evans, {W E} and Klein, {T E} and {Clinical Pharmacogenetics Implementation Consortium}",

year = "2011",

doi = "10.1038/clpt.2010.320",

language = "English",

volume = "89",

pages = "387--91",

journal = "Clinical Pharmacology and Therapeutics",

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T1 - Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing

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

PY - 2011

Y1 - 2011

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.

KW - 6-Mercaptopurine

KW - Antimetabolites, Antineoplastic

KW - Azathioprine

KW - Dose-Response Relationship, Drug

KW - Genotype

KW - Humans

KW - Immunosuppressive Agents

KW - Methyltransferases

KW - Thioguanine

U2 - 10.1038/clpt.2010.320

DO - 10.1038/clpt.2010.320

M3 - Journal article

C2 - 21270794

SN - 0009-9236

VL - 89

SP - 387

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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