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

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Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Klein TE

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

Clin Pharmacol Ther. 2011 Mar;89(3):387-91. doi: 10.1038/clpt.2010.320. Epub 2011 Jan 26.

PubMed ID

21270794 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Tioguanine	Thiopurine S-methyltransferase Gene symbol: TPMT UniProt: P51580	TPMT*2	(G;G) / (C;G)	G Allele (rs1800462)	ADR Directly Studied	The presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine.	Details
Tioguanine	Thiopurine S-methyltransferase Gene symbol: TPMT UniProt: P51580	TPMT*3A	(A;A) / (A;G)	A Allele (rs1800460)	ADR Directly Studied	The presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine.	Details
Tioguanine	Thiopurine S-methyltransferase Gene symbol: TPMT UniProt: P51580	TPMT*3C	(G;G) / (A;G)	G Allele (rs1142345)	ADR Directly Studied	The presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine.	Details
Tioguanine	Thiopurine S-methyltransferase Gene symbol: TPMT UniProt: P51580	TPMT*4A	(A;A) / (A;G)	G > A (rs1800584)	ADR Directly Studied	The presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine.	Details