Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update

Mary V. Relling; Matthias Schwab; Michelle Whirl-Carrillo; Guilherme Suarez-Kurtz; Ching Hon Pui; Charles M. Stein; Ann M. Moyer; William E. Evans; Teri E. Klein; Federico Guillermo Antillon-Klussmann; Kelly E. Caudle; Motohiro Kato; Allen E.J. Yeoh; Kjeld Schmiegelow; Jun J. Yang

doi:10.1002/cpt.1304

Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update

Mary V. Relling, Matthias Schwab, Michelle Whirl-Carrillo, Guilherme Suarez-Kurtz, Ching Hon Pui, Charles M. Stein, Ann M. Moyer, William E. Evans, Teri E. Klein, Federico Guillermo Antillon-Klussmann, Kelly E. Caudle, Motohiro Kato, Allen E.J. Yeoh, Kjeld Schmiegelow, Jun J. Yang^*

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

130 Citationer (Scopus)

Abstract

Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org).

Originalsprog	Engelsk
Tidsskrift	Clinical Pharmacology and Therapeutics
Vol/bind	105
Udgave nummer	5
Sider (fra-til)	1095-1105
Antal sider	11
ISSN	0009-9236
DOI	https://doi.org/10.1002/cpt.1304
Status	Udgivet - 2019

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10.1002/cpt.1304

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Relling, M. V., Schwab, M., Whirl-Carrillo, M., Suarez-Kurtz, G., Pui, C. H., Stein, C. M., Moyer, A. M., Evans, W. E., Klein, T. E., Antillon-Klussmann, F. G., Caudle, K. E., Kato, M., Yeoh, A. E. J., Schmiegelow, K., & Yang, J. J. (2019). Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clinical Pharmacology and Therapeutics, 105(5), 1095-1105. https://doi.org/10.1002/cpt.1304

Relling, MV, Schwab, M, Whirl-Carrillo, M, Suarez-Kurtz, G, Pui, CH, Stein, CM, Moyer, AM, Evans, WE, Klein, TE, Antillon-Klussmann, FG, Caudle, KE, Kato, M, Yeoh, AEJ, Schmiegelow, K & Yang, JJ 2019, 'Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update', Clinical Pharmacology and Therapeutics, bind 105, nr. 5, s. 1095-1105. https://doi.org/10.1002/cpt.1304

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title = "Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update",

abstract = "Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org).",

author = "Relling, {Mary V.} and Matthias Schwab and Michelle Whirl-Carrillo and Guilherme Suarez-Kurtz and Pui, {Ching Hon} and Stein, {Charles M.} and Moyer, {Ann M.} and Evans, {William E.} and Klein, {Teri E.} and Antillon-Klussmann, {Federico Guillermo} and Caudle, {Kelly E.} and Motohiro Kato and Yeoh, {Allen E.J.} and Kjeld Schmiegelow and Yang, {Jun J.}",

note = "This article also appears in: CPIC Guidelines Precision Medicine ",

year = "2019",

doi = "10.1002/cpt.1304",

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T2 - 2018 Update

AU - Relling, Mary V.

AU - Schwab, Matthias

AU - Whirl-Carrillo, Michelle

AU - Suarez-Kurtz, Guilherme

AU - Pui, Ching Hon

AU - Stein, Charles M.

AU - Moyer, Ann M.

AU - Evans, William E.

AU - Klein, Teri E.

AU - Antillon-Klussmann, Federico Guillermo

AU - Caudle, Kelly E.

AU - Kato, Motohiro

AU - Yeoh, Allen E.J.

AU - Schmiegelow, Kjeld

AU - Yang, Jun J.

N1 - This article also appears in: CPIC Guidelines Precision Medicine

PY - 2019

Y1 - 2019

N2 - Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org).

AB - Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org).

U2 - 10.1002/cpt.1304

DO - 10.1002/cpt.1304

M3 - Journal article

C2 - 30447069

AN - SCOPUS:85058034477

SN - 0009-9236

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SP - 1095

EP - 1105

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

IS - 5

ER -

Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update

Abstract

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