Ford Loretta, Kampanis Petros, Berg Jonathan
Department of Clinical Biochemistry, City Hospital, Birmingham, UK.
Ann Clin Biochem. 2009 Mar;46(Pt 2):152-4. doi: 10.1258/acb.2008.008167. Epub 2009 Jan 22.
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.
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.
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.
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.
作为我们硫嘌呤甲基转移酶（TPMT）表型分析服务质量控制系统的一部分，我们监测TPMT活性缺乏和低下的患者样本的基因型-表型一致性。我们研究了过去一年的基因型-表型一致性，以证明其作为质量保证工具的有效性。
2007年7月至2008年7月，对所有使用我们的表型分析方法且活性≤40 nmol 6-甲基巯基鸟嘌呤（6-MTG）/g血红蛋白/h进行分析的常规样本进行TPMT基因分型。计算每月的基因型-表型一致性，包括：所有TPMT活性缺乏结果与纯合突变体或复合杂合子基因型之间、TPMT活性低下与杂合子基因型之间、TPMT活性正常与野生型基因型之间。
共对14832个样本进行了TPMT表型分析，其中1769个进行了基因分型。TPMT活性低下与突变杂合子基因型之间的月平均一致性为83%，范围在67%-90%之间。通过表型分析确定的TPMT活性缺乏个体有44例。其中2例个体仅检测到一个突变等位基因，1例未鉴定出常见突变。
监测基因型-表型一致性是TPMT表型分析的一种有效质量保证工具。如本研究所示，目前的基因分型检测有遗漏一些缺乏患者的风险。
