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Genotyping should be considered the primary choice for pre-treatment evaluation of thiopurine methyltransferase function.

Hindorf, Ulf LU and Appell, Malin Lindqvist (2011) In Journal of Crohn's & Colitis 6(6). p.655-659
Abstract
BACKGROUND AND AIMS: A pre-treatment determination of the thiopurine S-methyltransferase (TPMT) genotype or phenotype can identify patients at risk of developing severe adverse reactions from thiopurine treatment. The risk of misclassifying a patient might be dependent on the method used. The aim of this study was to investigate the concordance between TPMT genotyping and phenotyping.



METHODS: The data consist of 7195 unselected and consecutive TPMT genotype and phenotype determinations sent to the division of Clinical Pharmacology, Linköping, Sweden. TPMT activity was measured in red blood cells (RBC) and the genotype determined by pyrosequencing for the three most common TPMT variants (TPMT *2, *3A, *3C).

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BACKGROUND AND AIMS: A pre-treatment determination of the thiopurine S-methyltransferase (TPMT) genotype or phenotype can identify patients at risk of developing severe adverse reactions from thiopurine treatment. The risk of misclassifying a patient might be dependent on the method used. The aim of this study was to investigate the concordance between TPMT genotyping and phenotyping.



METHODS: The data consist of 7195 unselected and consecutive TPMT genotype and phenotype determinations sent to the division of Clinical Pharmacology, Linköping, Sweden. TPMT activity was measured in red blood cells (RBC) and the genotype determined by pyrosequencing for the three most common TPMT variants (TPMT *2, *3A, *3C).



RESULTS: TPMT genotyping identified 89% as TPMT wild type (*1/*1), 10% as TPMT heterozygous and 0.5% as TMPT defective. The overall concordance between genotyping and phenotyping was 95%, while it was 96% among IBD patients (n=4024). Genotyping would have misclassified 8% of the TPMT defectives as heterozygous as compared to 11% if only TPMT activity had been measured. 11% of the heterozygous patients had a normal TPMT activity (>8.9U/ml RBC) and 3% of the TPMT wild-type patients had an intermediate TPMT activity (2.5-8.9U/ml RBC).



CONCLUSIONS: There is a risk for TPMT misclassification when only genotyping or phenotyping is used, but it is not reasonable to check both in all patients. Since TPMT genotyping is the more reliable test, especially in TPMT heterozygotes, we suggest that genotyping should be considered the primary choice for the pre-treatment evaluation of TPMT function before initiation of thiopurine therapy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Crohn's & Colitis
volume
6
issue
6
pages
655 - 659
publisher
Elsevier
external identifiers
  • wos:000305874000003
  • pmid:22398041
  • scopus:84862170980
ISSN
1873-9946
DOI
10.1016/j.crohns.2011.11.014
language
English
LU publication?
yes
id
06373b26-6830-4254-9bbc-5a343486f841 (old id 2432170)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22398041?dopt=Abstract
date added to LUP
2012-04-03 09:04:49
date last changed
2017-09-17 04:04:53
@article{06373b26-6830-4254-9bbc-5a343486f841,
  abstract     = {BACKGROUND AND AIMS: A pre-treatment determination of the thiopurine S-methyltransferase (TPMT) genotype or phenotype can identify patients at risk of developing severe adverse reactions from thiopurine treatment. The risk of misclassifying a patient might be dependent on the method used. The aim of this study was to investigate the concordance between TPMT genotyping and phenotyping. <br/><br>
<br/><br>
METHODS: The data consist of 7195 unselected and consecutive TPMT genotype and phenotype determinations sent to the division of Clinical Pharmacology, Linköping, Sweden. TPMT activity was measured in red blood cells (RBC) and the genotype determined by pyrosequencing for the three most common TPMT variants (TPMT *2, *3A, *3C). <br/><br>
<br/><br>
RESULTS: TPMT genotyping identified 89% as TPMT wild type (*1/*1), 10% as TPMT heterozygous and 0.5% as TMPT defective. The overall concordance between genotyping and phenotyping was 95%, while it was 96% among IBD patients (n=4024). Genotyping would have misclassified 8% of the TPMT defectives as heterozygous as compared to 11% if only TPMT activity had been measured. 11% of the heterozygous patients had a normal TPMT activity (&gt;8.9U/ml RBC) and 3% of the TPMT wild-type patients had an intermediate TPMT activity (2.5-8.9U/ml RBC). <br/><br>
<br/><br>
CONCLUSIONS: There is a risk for TPMT misclassification when only genotyping or phenotyping is used, but it is not reasonable to check both in all patients. Since TPMT genotyping is the more reliable test, especially in TPMT heterozygotes, we suggest that genotyping should be considered the primary choice for the pre-treatment evaluation of TPMT function before initiation of thiopurine therapy.},
  author       = {Hindorf, Ulf and Appell, Malin Lindqvist},
  issn         = {1873-9946},
  language     = {eng},
  number       = {6},
  pages        = {655--659},
  publisher    = {Elsevier},
  series       = {Journal of Crohn's & Colitis},
  title        = {Genotyping should be considered the primary choice for pre-treatment evaluation of thiopurine methyltransferase function.},
  url          = {http://dx.doi.org/10.1016/j.crohns.2011.11.014},
  volume       = {6},
  year         = {2011},
}