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4 edition of Thiopurine methyltransferase pharmacogenetics found in the catalog.

Thiopurine methyltransferase pharmacogenetics

Colleen M. Leo

Thiopurine methyltransferase pharmacogenetics

by Colleen M. Leo

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  • 6 Currently reading

Published by National Library of Canada = Bibliothèque nationale du Canada in Ottawa .
Written in English


Edition Notes

SeriesCanadian theses = Thèses canadiennes
The Physical Object
FormatMicroform
Pagination2 microfiches : negative.
ID Numbers
Open LibraryOL14726055M
ISBN 100315740558
OCLC/WorldCa30071224

Identification of two novel sequence variants affecting thiopurine methyltransferase enzyme activity. Pharmacogenetics , IV. Malin Lindqvist, Ulf Hindorf, Sven Almer, Peter Söderkvist, Magnus Ström, Henrik Hjortswang and Curt Peterson. Pharmacogenetics during initiation of thiopurine treatment in inflammatory bowel by: 3. Thiopurine Methyltransferase. The genetic polymorphism in the thiopurine methyltransferase (TPMT) gene first reported by Weinshilboum et al. in is widely viewed as the first clinically important example of a pharmacogenetic variant. The basis for this lies in the important clinical consequences of this relatively rare polymorphism.

Thiopurine pharmacogenetics in leukemia: Correlation of erythrocyte thiopurine methyltransferase activity and 6‐thioguanine nucleotide concentrations Lynne Lennard PhD University Department of Therapeutics, the Royal Hallamshire Hospital, the Clinical Pharmacology Unit, Department of Pharmacology, Mayo Clinic/Mayo FoundationCited by: Javascript Is Disabled! PharmGKB requires Missing: book.

Thiopurine methyltransferase (TPMT) is an enzyme that breaks down (metabolizes) a class of drugs called thiopurines. These drugs are used to suppress the immune system and are prescribed to treat various immune-related conditions or blood disorders (e.g., leukemia).The activity level of the TPMT enzyme, or the genetics underlying the enzyme's activity, is tested before thiopurine drug therapy Missing: book. Thiopurine methyltransferase methylates thiopurine compounds. The methyl donor is S-adenosyl-L-methionine, which is converted to enzyme metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct.. Clinical significance. Thiopurine drugs such as 6-mercaptopurine are used as Aliases: TPMT, entrez, TPMTD, thiopurine S .


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Thiopurine methyltransferase pharmacogenetics by Colleen M. Leo Download PDF EPUB FB2

CLINICAL SIGNIFICANCE OF TPMT. TPMT is a cytosolic enzyme (E.C. ) with the highest levels in heart and liver and relatively low levels in brain and lungs [].It catalyses the S-methylation of aromatic and heterocyclic sulphydryl compounds including anticancer and immunosuppressive thiopurine drugs, which are Azathioprine (AZA), 6-mercaptopurine (6MP) and 6-thioguanine (6TG) [].Cited by:   Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.

Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Klein TE, et al. Clin Pharmacol Ther. Mar; 89(3)Cited by: 2. Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine dual variation in the toxicity and therapeutic efficacy of these drugs is associated with a common genetic polymorphism that controls levels of TPMT activity and immunoreactive protein in Cited by: Thiopurine methyltransferase (TPMT) activity shows significant interindividual variation, with approximately 90% of individuals having high (wild-type) activity, Thiopurine methyltransferase pharmacogenetics book with intermediate activity.

Pharmacogenomics is a burgeoning field aimed at elucidating the genetic basis of differences in drug efficacy and toxicity, using genome-wide approaches to identify the network of genes that govern an individual’s response to drug therapy.

For some genetic polymorphisms, such as thiopurine S-methyltransferase (TPMT), monogenic traits have a marked effect on the pharmacokinetics of. Thiopurine S-methyltransferase (TPMT, S-adenosyl-l-methionine: thiopurine S-methyltransferase; EC ) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP) and azathioprine as well as other aromatic and heterocyclic sulfhydryl compounds [1,2].Weinshilboum and Sladek [] reported trimodality for level of red cell TPMT among randomly selected Caucasians: Cited by: Wang L, Nguyen TV, McLaughlin RW, Sikkink LA, Ramirez-Alvarado M, et al.

Human thiopurine S-methyltransferase pharmacogenetics: variant allozyme misfolding and aggresome formation. Proc Natl Acad Sci U S A ; DOI PubMed PMC;   The thiopurine S -methyltransferase (TPMT) genetic polymorphism is one of the most ‘mature’ examples in by: Thiopurine methyltransferase status and thiopurine drug dose As noted previously, some thiopurine adverse effects are related to the concentrations of metabolites.

However, a number of studies have shown that thiopurine drug dose does not correlate well with 6‐TGN concentration. 11, 44 Despite this, many clinicians continue to use empiric Cited by: Thiopurine S-methyltransferase (TPMT) genetic polymorphisms represent a striking example of the clinical importance of pharmacogenetics.TPMT also represents a model system for the study of pharmacogenetic functional mechanisms – especially mechanisms involving nonsynonymous SNPs – polymorphisms that alter the encoded amino acid sequence.

Cited by:   Thiopurines are often the mainstay of treatment for many patients with inflammatory bowel disease. As such, a general understanding of the evidence behind their use and of their metabolism is extremely useful in clinical practice. This review gives a practical overview of thiopurine metabolism, the importance of thiopurine S-methyltransferase testing prior to the start of therapy and the Cited by: The thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used in the consolidation and maintenance phases of treatment protocols for childhood acute lymphoblastic leukemia (ALL) [].

6-MP is the established thiopurine in the maintenance phase; when used during maintenance therapy 6-TG carries a greater risk of severe adverse effects [2,3] but, it may be more effective for Cited by: Pharmacogenetics of thiopurines in pediatric ALL is very well studied.

Table 1 summarizes the genetic factors involved in thiopurine toxicities and further discussed in t his review: T PMT varia. DOI: / Corpus ID: Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy.

@article{EvansPharmacogeneticsOT, title={Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy.}, author={Williams E Evans}, journal={Therapeutic drug monitoring}, year={}, volume={26 2}. Brahe, P. Bannetta, P. Meera Khan, F. Arwert, A. SerraAssignment of the catechol O-methyltransferase gene to human chromosome 22 in somatic cell hybrids.

Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the Missing: book.

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 Cited by: Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine dosing based on TPMT and NUDT15 genotypes: Update (November ) Updates since publication: April The authors of this guideline have added recommendations for TPMT and NUDT15 indeterminate phenotypes (i.e.

combination of uncertain and/or unknown function alleles). Missing: book. Measurement of thiopurine methyltransferase (TPMT) status, prior to the start of azathioprine therapy, has a role in identifying the TPMT deficient patient at risk of severe myelosuppression and TPMT heterozygous individuals who are prone to early myelosuppression.

1, 2 The risk of azathioprine toxicity is well recognised but, as the authors state, the duration of early monitoring is a matter Cited by:   Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.

Clin Pharmacol Ther. Mar;89(3) doi: /clpt Epub Jan. Schaeffeler E, Fischer C, Brockmeier D et al () Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants.

Pharmacogenetics – CrossRef PubMed Google ScholarCited by: Otterness D, Szumlanski C, Wood T, Lennard L, Klemetsdal B, Aarbakke J et al. Thiopurine methyltransferase (TPMT) pharmacogenetics: Polymorphism characterization. Clinical pharmacology and therapeutics.

Dec 1;61(2).Author: D. Otterness, C. Szumlanski, T. Wood, L. Lennard, B. Klemetsdal, J. Aarbakke, J. Park-Hah, H. Iven. Thiopurine drugs are used to treat patients with neoplasia and autoimmune disease as well as transplant recipients.

These agents are metabolized, in part, by S -methylation catalyzed by thiopurine methyltransferase (TPMT). The discovery nearly two decades ago that levels of TPMT activity in human tissues are controlled by a common genetic polymorphism led to one of the best Cited by: