BACKGROUND: As part of the quality control system for our TPMT phenotyping service we monitor the genotype-phenotype concordance for patient samples with deficient and low TPMT activity. We have studied the genotype-phenotype concordance over the last year to demonstrate its effectiveness as a quality assurance tool. METHODS: From July 2007 to July 2008 TPMT genotyping was performed on all routine samples analysed using our phenotypic assay with an activity of <or=40 nmol 6-MTG/gHb/h. The monthly genotype-phenotype concordance was calculated between: all deficient TPMT activity results and a homozygous mutant or compound heterozygote genotype, low TPMT activity and a heterozygote genotype, normal TPMT activity and a wild-type genotype. RESULTS: A total of 14,832 samples were analysed by TPMT phenotyping and 1769 of these by genotyping. The monthly mean concordance between low TPMT activity and a mutant heterozygote genotype was 83%, ranging from 67-90%. The number of individuals with deficient TPMT activity identified by phenotyping was 44. For two of these individuals only one mutant allele was detected, and for one no common mutations were identified. CONCLUSIONS: Monitoring the genotype-phenotype concordance is an effective quality assurance tool for the TPMT phenotyping assay. As demonstrated in this study current genotyping assays risk missing some deficient patients.
BACKGROUND: As part of the quality control system for our TPMT phenotyping service we monitor the genotype-phenotype concordance for patient samples with deficient and low TPMT activity. We have studied the genotype-phenotype concordance over the last year to demonstrate its effectiveness as a quality assurance tool. METHODS: From July 2007 to July 2008 TPMT genotyping was performed on all routine samples analysed using our phenotypic assay with an activity of <or=40 nmol 6-MTG/gHb/h. The monthly genotype-phenotype concordance was calculated between: all deficient TPMT activity results and a homozygous mutant or compound heterozygote genotype, low TPMT activity and a heterozygote genotype, normal TPMT activity and a wild-type genotype. RESULTS: A total of 14,832 samples were analysed by TPMT phenotyping and 1769 of these by genotyping. The monthly mean concordance between low TPMT activity and a mutant heterozygote genotype was 83%, ranging from 67-90%. The number of individuals with deficient TPMT activity identified by phenotyping was 44. For two of these individuals only one mutant allele was detected, and for one no common mutations were identified. CONCLUSIONS: Monitoring the genotype-phenotype concordance is an effective quality assurance tool for the TPMT phenotyping assay. As demonstrated in this study current genotyping assays risk missing some deficient patients.
Authors: Lilla M Roy; Richard M Zur; Elizabeth Uleryk; Chris Carew; Shinya Ito; Wendy J Ungar Journal: Pharmacogenomics Date: 2016-03-29 Impact factor: 2.533
Authors: José A G Agúndez; Jaime Del Barrio; Teresa Padró; Camilla Stephens; Magí Farré; Raúl J Andrade; Lina Badimon; Elena García-Martín; Gemma Vilahur; M Isabel Lucena Journal: Front Pharmacol Date: 2012-01-19 Impact factor: 5.810