EVALUATION OF THE ACCURACY OF THE ARRAY METHOD FOR ANALYSIS OF COPY NUMBER VARIATIONS (CNVs) IN THE CYP2D6 GENE

• Grant number: 25/07105-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Carolina Dagli Hernandez
• Grantee: Alice Cordeiro dos Santos Correia
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Introduction: The CYP2D6 gene encodes a cytochrome P450 enzyme responsible for the metabolism of approximately 20% of clinically used drugs, including antineoplastics and opioids. Genetic variations in this gene influence the metabolic phenotype, allowing individuals to be classified as poor, intermediate, normal, or ultrarapid metabolizers. The analysis of copy number variations (CNVs) in the CYP2D6 gene is particularly important for identifying ultrarapid metabolizers and non-functional hybrid alleles involving CYP2D6 and its neighboring pseudogene, CYP2D7. Accurate characterization of CNVs is essential for the implementation of pharmacogenetics in clinical practice. Among the available genotyping methods, array-based genotyping shows potential for detecting CNVs and hybrids but still requires validation against established methodologies, such as quantitative real-time polymerase chain reaction (qPCR).Objective: To evaluate the accuracy of array-based genotyping for the detection of CNVs in CYP2D6.Materials and Methods: Patients with CNVs or hybrid alleles in CYP2D6, previously identified by array in studies conducted by the CliPhar laboratory (UNICAMP), will be included. DNA was extracted from whole blood or buccal swabs. Genotyping by array was performed using the Infinium Global Diversity Array with Enhanced PGx. qPCR genotyping will be carried out using TaqMan probes specific for the 5'-UTR and exon 9 regions of CYP2D6. Data obtained from both techniques will be compared through concordance analysis, using Cohen's kappa coefficient for categorical variables and intraclass correlation for continuous measures. The study was approved by the Research Ethics Committees of UNICAMP and INCA.