The pharmacogenetic basis of individual variation in thiopurine metabolism

Paul Andrew Blaker; Monica Arenas-Hernandez; Anthony Marin Marinaki; Jeremy Sanderson

doi:10.2217/PME.12.85

The pharmacogenetic basis of individual variation in thiopurine metabolism

Paul Andrew Blaker^*, Monica Arenas-Hernandez, Anthony Marin Marinaki, Jeremy Sanderson

^*Corresponding author for this work

King's College London

GSTT Guy's and St Thomas' NHS Foundation Trust

Research output: Contribution to journal › Literature review › peer-review

14 Citations (Scopus)

Abstract

Thiopurines are an important class of immunosuppressive therapy, which have been used in clinical practice for over 50 years. Despite this extensive experience many of the pharmacodynamic and pharmacokinetic properties of these drugs remain unknown. As a consequence there is often no clear explanation for the individual variation in response to treatment, both in terms of efficacy or adverse drug reactions. This review, which emphasizes practice in gastroenterology, summarizes the current understanding of thiopurine drug metabolism and highlights the role of nongenetic and genetic factors other than TPMT, which should be a focus for future research. Correlation of polymorphic variations in these genes with clinical outcomes is expected to clarify the basis for interindividual differences in thiopurine metabolism and enable a more personalized approach to therapy.

Original language	English
Pages (from-to)	707-725
Number of pages	19
Journal	Personalized Medicine
Volume	9
Issue number	7
DOIs	https://doi.org/10.2217/PME.12.85
Publication status	Published - Sept 2012

Keywords

azathioprine
genetic
interindividual variation
mercaptopurine
metabolism
pharmacogenetics
thiopurine
INFLAMMATORY-BOWEL-DISEASE
ACUTE LYMPHOBLASTIC-LEUKEMIA
INOSINE-TRIPHOSPHATE-PYROPHOSPHATASE
METHYLTRANSFERASE TPMT GENE
GLUTATHIONE-S-TRANSFERASE
6-THIOGUANINE NUCLEOTIDE CONCENTRATIONS
SYSTEMIC-LUPUS-ERYTHEMATOSUS
NON-HODGKIN-LYMPHOMA
RED-BLOOD-CELLS
CROHNS-DISEASE

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title = "The pharmacogenetic basis of individual variation in thiopurine metabolism",

abstract = "Thiopurines are an important class of immunosuppressive therapy, which have been used in clinical practice for over 50 years. Despite this extensive experience many of the pharmacodynamic and pharmacokinetic properties of these drugs remain unknown. As a consequence there is often no clear explanation for the individual variation in response to treatment, both in terms of efficacy or adverse drug reactions. This review, which emphasizes practice in gastroenterology, summarizes the current understanding of thiopurine drug metabolism and highlights the role of nongenetic and genetic factors other than TPMT, which should be a focus for future research. Correlation of polymorphic variations in these genes with clinical outcomes is expected to clarify the basis for interindividual differences in thiopurine metabolism and enable a more personalized approach to therapy.",

keywords = "azathioprine, genetic, interindividual variation, mercaptopurine, metabolism, pharmacogenetics, thiopurine, INFLAMMATORY-BOWEL-DISEASE, ACUTE LYMPHOBLASTIC-LEUKEMIA, INOSINE-TRIPHOSPHATE-PYROPHOSPHATASE, METHYLTRANSFERASE TPMT GENE, GLUTATHIONE-S-TRANSFERASE, 6-THIOGUANINE NUCLEOTIDE CONCENTRATIONS, SYSTEMIC-LUPUS-ERYTHEMATOSUS, NON-HODGKIN-LYMPHOMA, RED-BLOOD-CELLS, CROHNS-DISEASE",

author = "Blaker, {Paul Andrew} and Monica Arenas-Hernandez and Marinaki, {Anthony Marin} and Jeremy Sanderson",

year = "2012",

month = sep,

doi = "10.2217/PME.12.85",

language = "English",

volume = "9",

pages = "707--725",

journal = "Personalized Medicine",

issn = "1741-0541",

publisher = "Future Medicine",

number = "7",

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T1 - The pharmacogenetic basis of individual variation in thiopurine metabolism

AU - Blaker, Paul Andrew

AU - Arenas-Hernandez, Monica

AU - Marinaki, Anthony Marin

AU - Sanderson, Jeremy

PY - 2012/9

Y1 - 2012/9

N2 - Thiopurines are an important class of immunosuppressive therapy, which have been used in clinical practice for over 50 years. Despite this extensive experience many of the pharmacodynamic and pharmacokinetic properties of these drugs remain unknown. As a consequence there is often no clear explanation for the individual variation in response to treatment, both in terms of efficacy or adverse drug reactions. This review, which emphasizes practice in gastroenterology, summarizes the current understanding of thiopurine drug metabolism and highlights the role of nongenetic and genetic factors other than TPMT, which should be a focus for future research. Correlation of polymorphic variations in these genes with clinical outcomes is expected to clarify the basis for interindividual differences in thiopurine metabolism and enable a more personalized approach to therapy.

AB - Thiopurines are an important class of immunosuppressive therapy, which have been used in clinical practice for over 50 years. Despite this extensive experience many of the pharmacodynamic and pharmacokinetic properties of these drugs remain unknown. As a consequence there is often no clear explanation for the individual variation in response to treatment, both in terms of efficacy or adverse drug reactions. This review, which emphasizes practice in gastroenterology, summarizes the current understanding of thiopurine drug metabolism and highlights the role of nongenetic and genetic factors other than TPMT, which should be a focus for future research. Correlation of polymorphic variations in these genes with clinical outcomes is expected to clarify the basis for interindividual differences in thiopurine metabolism and enable a more personalized approach to therapy.

KW - azathioprine

KW - genetic

KW - interindividual variation

KW - mercaptopurine

KW - metabolism

KW - pharmacogenetics

KW - thiopurine

KW - INFLAMMATORY-BOWEL-DISEASE

KW - ACUTE LYMPHOBLASTIC-LEUKEMIA

KW - INOSINE-TRIPHOSPHATE-PYROPHOSPHATASE

KW - METHYLTRANSFERASE TPMT GENE

KW - GLUTATHIONE-S-TRANSFERASE

KW - 6-THIOGUANINE NUCLEOTIDE CONCENTRATIONS

KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS

KW - NON-HODGKIN-LYMPHOMA

KW - RED-BLOOD-CELLS

KW - CROHNS-DISEASE

U2 - 10.2217/PME.12.85

DO - 10.2217/PME.12.85

M3 - Literature review

SN - 1741-0541

VL - 9

SP - 707

EP - 725

JO - Personalized Medicine

JF - Personalized Medicine

IS - 7

ER -

The pharmacogenetic basis of individual variation in thiopurine metabolism

Abstract

Keywords

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