Guigao Lin1,2, Xiao Zhang3, Kuo Zhang1,2, Yanxi Han1,2, Liming Tan3, Jinming Li1,2. 1. National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China. 2. Beijing Engineering Research Center of Laboratory Medicine, Beijing, China. 3. Department of Laboratory, The People's Hospital of Hunan Province, First Affiliated Hospital of Hunan Normal University, Changsha, China.
Abstract
BACKGROUND: Tacrolimus is the most widely used immunosuppressant in solid organ transplant patients. The cytochrome P450 3A5 (CYP3A5) has been proved to be associated with tacrolimus dose requirement. Molecular detection for CYP3A5 genotyping is demanded for the optimization of treatments of tacrolimus. METHODS: To achieve the consistency and accuracy of the testing results, the Chinese National Center for Clinical Laboratories (NCCL) organized a national external quality assessment(EQA) program to evaluate the performance of laboratories providing CYP3A5 genotyping. Ten validated DNA samples covering the common genetic polymorphisms of CYP3A5 were delivered to 33 voluntary laboratories, and their detecting results and clinical written reports were evaluated. RESULTS: Thirty-three datasets were received. The corresponding analytical sensitivity was 95.9% (285/297 challenges; 95% confidence interval: 93.0%-97.9%), and the analytical specificity was 95.3% (346/363; 95% confidence interval: 92.6%-97.2%). Thirty of the participating laboratories correctly identified the CYP3A5 allele status for all EQA samples. Three laboratories made genotyping errors, and 2 of them failed to detect any of the homozygotes such as *1/*1 and *3/*3. Twenty-eight CYP3A5*3 tests reports were submitted, but many reports showed a shortage of essential information. No reports fulfilled all the consensus recommendations for pharmacogenetic test result reporting. CONCLUSION: The EQA program highlighted the necessity for an improvement in the accuracy of genotyping for some of the laboratories and a greater education on the reporting of CYP3A5 genotyping results.
BACKGROUND:Tacrolimus is the most widely used immunosuppressant in solid organ transplant patients. The cytochrome P450 3A5 (CYP3A5) has been proved to be associated with tacrolimus dose requirement. Molecular detection for CYP3A5 genotyping is demanded for the optimization of treatments of tacrolimus. METHODS: To achieve the consistency and accuracy of the testing results, the Chinese National Center for Clinical Laboratories (NCCL) organized a national external quality assessment(EQA) program to evaluate the performance of laboratories providing CYP3A5 genotyping. Ten validated DNA samples covering the common genetic polymorphisms of CYP3A5 were delivered to 33 voluntary laboratories, and their detecting results and clinical written reports were evaluated. RESULTS: Thirty-three datasets were received. The corresponding analytical sensitivity was 95.9% (285/297 challenges; 95% confidence interval: 93.0%-97.9%), and the analytical specificity was 95.3% (346/363; 95% confidence interval: 92.6%-97.2%). Thirty of the participating laboratories correctly identified the CYP3A5 allele status for all EQA samples. Three laboratories made genotyping errors, and 2 of them failed to detect any of the homozygotes such as *1/*1 and *3/*3. Twenty-eight CYP3A5*3 tests reports were submitted, but many reports showed a shortage of essential information. No reports fulfilled all the consensus recommendations for pharmacogenetic test result reporting. CONCLUSION: The EQA program highlighted the necessity for an improvement in the accuracy of genotyping for some of the laboratories and a greater education on the reporting of CYP3A5 genotyping results.
Authors: P Kuehl; J Zhang; Y Lin; J Lamba; M Assem; J Schuetz; P B Watkins; A Daly; S A Wrighton; S D Hall; P Maurel; M Relling; C Brimer; K Yasuda; R Venkataramanan; S Strom; K Thummel; M S Boguski; E Schuetz Journal: Nat Genet Date: 2001-04 Impact factor: 38.330
Authors: A B Santoro; C J Struchiner; C R Felipe; H Tedesco-Silva; J O Medina-Pestana; G Suarez-Kurtz Journal: Clin Pharmacol Ther Date: 2013-04-02 Impact factor: 6.875
Authors: J T Tang; L M Andrews; T van Gelder; Y Y Shi; R H N van Schaik; L L Wang; D A Hesselink Journal: Expert Opin Drug Metab Toxicol Date: 2016-04-07 Impact factor: 4.481
Authors: K A Birdwell; B Decker; J M Barbarino; J F Peterson; C M Stein; W Sadee; D Wang; A A Vinks; Y He; J J Swen; J S Leeder; Rhn van Schaik; K E Thummel; T E Klein; K E Caudle; I A M MacPhee Journal: Clin Pharmacol Ther Date: 2015-06-03 Impact factor: 6.875
Authors: Adam S Gordon; Robert S Fulton; Xiang Qin; Elaine R Mardis; Deborah A Nickerson; Steve Scherer Journal: Pharmacogenet Genomics Date: 2016-04 Impact factor: 2.089
Authors: Vincent Haufroid; Michel Mourad; Valérie Van Kerckhove; Jeremie Wawrzyniak; Martine De Meyer; Djamila Chaib Eddour; Jacques Malaise; Dominique Lison; Jean-Paul Squifflet; Pierre Wallemacq Journal: Pharmacogenetics Date: 2004-03
Authors: Ee Mun Lim; Ken A Sikaris; Janice Gill; John Calleja; Peter E Hickman; John Beilby; Samuel D Vasikaran Journal: Clin Chem Date: 2004-03 Impact factor: 8.327
Authors: Kelly E Caudle; Henry M Dunnenberger; Robert R Freimuth; Josh F Peterson; Jonathan D Burlison; Michelle Whirl-Carrillo; Stuart A Scott; Heidi L Rehm; Marc S Williams; Teri E Klein; Mary V Relling; James M Hoffman Journal: Genet Med Date: 2016-07-21 Impact factor: 8.822