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Design and implementation of a novel pharmacogenetic assay for the identification of the CYP2D6*10 genetic variant.

Title: Design and implementation of a novel pharmacogenetic assay for the identification of the CYP2D6*10 genetic variant.
Authors: Ranadeva NDK; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka. nadeeka@kiu.ac.lk.; Sirisena ND; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka.; Wetthasinghe TK; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka.; Noordeen N; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka.; Dissanayake VHW; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka.
Source: BMC research notes [BMC Res Notes] 2022 Mar 16; Vol. 15 (1), pp. 104. Date of Electronic Publication: 2022 Mar 16.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Biomed Central Country of Publication: England NLM ID: 101462768 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-0500 (Electronic) Linking ISSN: 17560500 NLM ISO Abbreviation: BMC Res Notes Subsets: MEDLINE
Imprint Name(s): Original Publication: London : Biomed Central, 2008.
MeSH Terms: Cytochrome P-450 CYP2D6*/genetics ; Cytochrome P-450 CYP2D6*/metabolism ; Pharmacogenetics*; Antineoplastic Agents, Hormonal/metabolism ; Tamoxifen/therapeutic use ; Female ; Genotype ; Humans
Abstract: Objectives: Tamoxifen is considered to be the most widely used adjuvant therapy for hormone receptor positive breast cancer in premenopausal women. However, it is reported that nearly 30% of patients receiving tamoxifen therapy have shown reduced or no benefits. This may be due to the high inter-individual variations in the CYP2D6 gene that is involved in tamoxifen metabolism. The CYP2D6*10 gene variant (rs1065852C>T) is reported to be commonly found in Asian and South Asian populations. The present study was undertaken to design a novel pharmacogenetic assay (Single step-Tetra Arms Polymerase Chain Reaction) for the identification of the CYP2D6*10 variant and implement the designed assay by genotyping a cohort of breast cancer patients.; Results: The novel assay was successfully designed, optimized and validated using Sanger sequencing. Blood samples from 70 patients were genotyped. The following bands were observed in the gel image: Control band at 454 bp; band for C allele at 195 bp; band for T allele at 300 bp. The genotype frequencies for the CYP2D6*10 (rs1065852C>T) variant were: CC-24.28% (17/70), CT-75.71% (53/70), TT-0% (0/70). The allele frequencies were: T-allele-37.86% and C-allele-62.14%.; (© 2022. The Author(s).)
References: BMC Res Notes. 2018 Feb 15;11(1):132. (PMID: 29448951); J Clin Lab Anal. 2020 Jan;34(1):e23005. (PMID: 31441095); Mol Biotechnol. 2014 Jul;56(7):599-608. (PMID: 24519268); Biomed Rep. 2018 Nov;9(5):446-452. (PMID: 30345040); Pharmacogenet Genomics. 2009 Jul;19(7):559-62. (PMID: 19512959); Pharmaceuticals (Basel). 2010 Apr 15;3(4):1122-1138. (PMID: 27713292); Methods Protoc. 2019 Jul 25;2(3):. (PMID: 31349745); Indian J Hum Genet. 2013 Oct;19(4):392-6. (PMID: 24497701); Int J Cancer. 2019 Apr 15;144(8):1941-1953. (PMID: 30350310)
Contributed Indexing: Keywords: Breast cancer; CYP2D6*10; Genotypes; Pharmacogenetics; Tamoxifen
Substance Nomenclature: 0 (Antineoplastic Agents, Hormonal); 094ZI81Y45 (Tamoxifen); EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
Entry Date(s): Date Created: 20220317 Date Completed: 20220318 Latest Revision: 20220324
Update Code: 20260130
PubMed Central ID: PMC8925205
DOI: 10.1186/s13104-022-05993-6
PMID: 35296326
Database: MEDLINE

Journal Article