CYP2D6 genotyping for functional-gene dosage analysis by allele copy number detection

73Citations
Citations of this article
62Readers
Mendeley users who have this article in their library.

Abstract

BACKGROUND: Cytochrome P450 2D6 (CYP2D6), one of the most important drug-metabolizing enzymes, has been reported to possess variation in the encoding CYP2D6 gene (cytochrome P450, family 2, subfamily D, polypeptide 6) that affects enzymatic activity. For the pharmacogenetic study of CYP2D6, accurate measurement of the dosage of the functional gene is essential; however, current genotyping techniques are insufficient because of their inability to provide the exact copy number of functional CYP2D6 genes. METHODS: We developed 3 quantitative real-time PCR (qPCR) assays for estimating the total copy number of the CYP2D6 gene, as well as 24-multiplex PCR-based real-time Invader assays (mPCR-RETINAs) for estimating the allele ratio at each variation locus. After determining the allele copy number at each locus, we estimated the frequencies of CYP2D6 alleles in a population and the diplotype in each individual by a CNVphaser (copy number variation phaser). The qPCR assays and RETINAs used for HapMap Japanese and Chinese samples were applied to 455 Japanese individuals. RESULTS: Forty-two individuals (9.2%) had one CYP2D6 gene copy, 207 (45.5%) had 2 copies, 161 (35.4%) had 3 copies, 40 (8.8%) had 4 copies, and 5 (1.1%) had 5 copies of the CYP2D6 gene. We found 16 different CYP2D6 alleles, with frequencies similar to those described in previous reports. In the diplotype analysis, we observed that CYP2D6*1/*1 and *1/*10- *36 were the most common diplotypes (approximately 20%) in our population. CONCLUSIONS: Our method is the first to determine the exact number of functional CYP2D6 gene copies. We believe our method will facilitate and accelerate the detailed pharmacogenetic analysis of CYP2D6. © 2009 American Association for Clinical Chemistry.

References Powered by Scopus

Analyzing real-time PCR data by the comparative C<inf>T</inf> method

21024Citations
N/AReaders
Get full text

The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments

12352Citations
N/AReaders
Get full text

Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): Clinical consequences, evolutionary aspects and functional diversity

970Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Population differences in major functional polymorphisms of pharmacokinetics/pharmacodynamics-related genes in Eastern Asians and Europeans: Implications in the clinical trials for novel drug development

214Citations
N/AReaders
Get full text

Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients

214Citations
N/AReaders
Get full text

Complexities of CYP2D6 gene analysis and interpretation

191Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Hosono, N., Kato, M., Kiyotani, K., Mushiroda, T., Takata, S., Sato, H., … Kubo, M. (2009). CYP2D6 genotyping for functional-gene dosage analysis by allele copy number detection. Clinical Chemistry, 55(8), 1546–1554. https://doi.org/10.1373/clinchem.2009.123620

Readers over time

‘11‘12‘13‘14‘15‘16‘17‘18‘19‘20‘21‘22‘23‘24036912

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 18

44%

Researcher 14

34%

Professor / Associate Prof. 7

17%

Lecturer / Post doc 2

5%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 16

36%

Medicine and Dentistry 13

30%

Biochemistry, Genetics and Molecular Bi... 12

27%

Pharmacology, Toxicology and Pharmaceut... 3

7%

Save time finding and organizing research with Mendeley

Sign up for free
0