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Ther Drug Monit. 2011 Apr;33(2):192-9. doi: 10.1097/FTD.0b013e31820810cd.

Systematic review of thiopurine methyltransferase genotype and enzymatic testing strategies.

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1
Department of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

Abstract

BACKGROUND:

An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more accurate testing for diagnosis and treatment. Thiopurine methyltransferase (TPMT) plays an important role in the metabolism of thiopurine drugs used in pediatric leukemia, rheumatoid arthritis, and inflammatory bowel disease. The objective was to review the literature systematically to ascertain the performance characteristics of current genotype and enzymatic testing technologies for TPMT.

METHODS:

A systematic review of the literature was conducted to describe TPMT testing technologies. Eligible studies evaluated either a TPMT genotype or TPMT phenotype technology in comparison to a reference standard and expressed results in terms of sensitivity and specificity or positive/negative predictive value. The laboratory technique was recorded, and the quality of the identified studies was assessed using a modified Critical Appraisal Skills Program tool.

RESULTS:

Seventeen studies were reviewed. The sensitivity and specificity of the genotype test ranged from 55% to 100% and from 94% to 100%, respectively. The sensitivity and specificity of the phenotype test ranged from 92% to 100% and from 86% to 98%, respectively. A variety of laboratory techniques were employed. Reviewed studies were of low methodological quality.

CONCLUSIONS:

The systematic review of TPMT test strategies found that available technologies demonstrated high values for sensitivity and specificity, however, there was a lack of a single gold standard and most studies were of poor quality. Disregard for study sample size and confounding factors such as concurrent medications and blood transfusions were the main contributors to low quality. There were also inconsistencies in the selection of a reference standard which complicated the interpretation of the findings.

PMID:
21240057
DOI:
10.1097/FTD.0b013e31820810cd
[Indexed for MEDLINE]
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