Dataset Information

CYP2D6 allele frequencies, copy number variants, and tandems in the population of Hong Kong.

ABSTRACT: BACKGROUND:CYP2D6 plays a crucial role in drug metabolism of several drugs. It is known to be highly polymorphic with enzymatic activity ranging from poor to ultrarapid metabolic rates. While the frequencies of CYP2D6 alleles are generally known in different Asian populations, data on frequencies of the copy number variations (CNV) and tandems in CYP2D6 in which they occur are less well studied in these populations. METHODS:A cohort of 800 consecutive, unrelated individuals were referred to Prenetics Limited (Prenetics) iGenes test by physicians in Hong Kong as part of their care with informed consent. These clinical samples were deidentified prior to further analysis. Genotyping and copy number determination of CYP2D6 were performed using target specific TaqMan® SNP genotyping and copy number assays. The phenotypes of CYP2D6 were predicted based on its genotypes and is dependent on the biallelic expression of alleles. RESULTS:Among the Asian group (n = 735, 92%), the observed frequency of CYP2D6*36-*10 tandems was 34.1%. We also identified duplication of CYP2D6 alleles in 86 (11.7%) individuals of the study cohort. The frequency of all CYP2D6 duplicated alleles was 154 (10.5%) while only 28 (1.9%) of the duplications were of functional alleles (ie CYP2D6*1 and CYP2D6*2). CONCLUSION:The present study provides a comprehensive analysis on the occurrences of CNV and tandems of the CYP2D6 gene in the Hong Kong population. The results contribute to the overall knowledge of pharmacogenomics and may accelerate the implementation of precision medicine in Asia.

SUBMITTER: Chan W

PROVIDER: S-EPMC6430334 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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CYP2D6 allele frequencies, copy number variants, and tandems in the population of Hong Kong.

Chan Wing W Li Man S MS Sundaram Senthil K SK Tomlinson Brian B Cheung Pik Y PY Tzang Chi H CH

Journal of clinical laboratory analysis 20180801 1

<h4>Background</h4>CYP2D6 plays a crucial role in drug metabolism of several drugs. It is known to be highly polymorphic with enzymatic activity ranging from poor to ultrarapid metabolic rates. While the frequencies of CYP2D6 alleles are generally known in different Asian populations, data on frequencies of the copy number variations (CNV) and tandems in CYP2D6 in which they occur are less well studied in these populations.<h4>Methods</h4>A cohort of 800 consecutive, unrelated individuals were r ...[more]

PMID: 30069923

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Project description:BackgroundCYP2D6 testing is increasingly used to guide drug therapy and thus, reliable methods are needed to test this complex and polymorphic gene locus. A particular challenge arises from the detection and interpretation of structural variants (SVs) including gene deletions, duplications, and hybrids with the CYP2D7 pseudogene. This study validated the Absolute Q™ platform for digital PCR-based CYP2D6 copy number variation (CNV) determination by comparing results to those obtained with a previously established method using the QX200 platform. In addition, protocols for streamlining CYP2D6 CNV testing were established and validated including the "One-pot" single-step restriction enzyme digestion and a multiplex assay simultaneously targeting the CYP2D6 5'UTR, intron 6, and exon 9 regions.MethodsGenomic DNA (gDNA) samples from Coriell (n = 13) and from blood, saliva, and liver tissue (n = 17) representing 0-6 copies were tested on the Absolute Q and QX200 platforms. Custom TaqMan™ copy number (CN) assays targeting CYP2D6 the 5'UTR, intron 6, and exon 9 regions and a reference gene assay (TERT or RNaseP) were combined for multiplexing by optical channel. In addition, two digestion methods (One-pot digestion and traditional) were assessed. Inconclusive CN values on the Absolute Q were resolved using an alternate reference gene and/or diluting gDNA.ResultsOverall, results between the two platforms and digestions methods were consistent. The "One-pot" digestion method and optically multiplexing up to three CYP2D6 regions yielded consistent result across DNA sample types and diverse SVs, reliably detecting up to 6 gene copies. Rare variation in reference genes were found to interfere with results and interpretation, which were resolved by using a different reference.ConclusionThe Absolute Q produced accurate and reliable CYP2D6 copy number results allowing for a streamlined and economical protocol using One-pot digestion and multiplexing three target regions. Protocols are currently being expanded to other pharmacogenes presenting with SVs/CNVs.

Dataset Information

CYP2D6 allele frequencies, copy number variants, and tandems in the population of Hong Kong.

Publications

CYP2D6 allele frequencies, copy number variants, and tandems in the population of Hong Kong.

Similar Datasets

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