Frequency of CYP2D6 Alleles Including Structural Variants in the United States

• Hauptverfasser: Andria L. Del Tredici (VerfasserIn), Alka Malhotra (VerfasserIn), Matthew Dedek (VerfasserIn), Frank Espin (VerfasserIn), Dan Roach (VerfasserIn), Guang-dan Zhu (VerfasserIn), Joseph Voland (VerfasserIn), Tanya A. Moreno (VerfasserIn)
• Format: Buch
• Veröffentlicht: Frontiers Media S.A., 2018-04-01T00:00:00Z.
• Schlagworte: article
• Online-Zugang: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2018.00305
• Keywords: CYP2D6; pharmacogenetics; drug metabolism; copy number variation; cytochrome P450; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 9 (2018)

The CYP2D6 gene encodes an enzyme important in the metabolism of many commonly used medications. Variation in CYP2D6 is associated with inter-individual differences in medication response, and genetic testing is used to optimize medication therapy. This report describes a retrospective study of CYP2D6 allele frequencies in a large population of 104,509 de-identified patient samples across all regions of the United States (US). Thirty-seven unique CYP2D6 alleles including structural variants were identified. A majority of these alleles had frequencies which matched published frequency data from smaller studies, while eight had no previously published frequencies. Importantly, CYP2D6 structural variants were observed in 13.1% of individuals and accounted for 7% of the total variants observed. The majority of structural variants detected (73%) were decreased-function or no-function alleles. As such, structural variants were found in approximately one-third (30%) of CYP2D6 poor metabolizers in this study. This is the first CYP2D6 study to evaluate, with a consistent methodology, both structural variants and single copy alleles in a large US population, and the results suggest that structural variants have a substantial impact on CYP2D6 function.