Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/14450
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Type: Journal article
Title: A new simple diagnostic assay for the identification of the major CYP2D6 genotypes by DNA sequencing analysis
Author: James, H.
Coller, J.
Gillis, D.
Bahnisch, J.
Sallustio, B.
Somogyi, A.
Citation: International Journal of Clinical Pharmacology and Therapeutics, 2004; 42(12):719-723
Publisher: Dustri-Verlag Dr Karl Feistle
Issue Date: 2004
ISSN: 0946-1965
Statement of
Responsibility: 
H.M. James, J.K. Coller, D. Gillis, J. Bahnisch, B.C. Sallustio and A.A. Somogyi
Abstract: AIM: To establish a method suitable for diagnostic genotyping of CYP2D6 alleles by DNA sequencing. METHODS: Initial PCR reactions were performed to specifically amplify exons 3, 4, 5 and 6 of the CYP2D6 gene using primers previously published. New primers were used to identify *2, *3, *4, *6, *7, *8, *9 and *41 in 2 sequencing reactions. Additional primers were designed for reverse sequencing in samples with 1 or 3 b.p. deletions. Previously published assays were used to detect *5, *10 and *16 alleles to complete genotype assignment. RESULTS: We reliably detected the nonfunctional alleles, *3, *4, *6, *7 and *8, which are associated with the poor metabolizer phenotype, and 2 important alleles associated with decreased enzyme activity, *9 and *41. Observed allele frequencies were comparable to those found previously in Caucasian populations. CONCLUSION: CYP2D6 genotype has been shown in previous clinical studies to be a good predictor of CYP2D6 phenotype and, therefore, related to therapeutic response and the risk of drug toxicity. This genotyping method is simple and reliable, and, therefore, can be routinely performed on an isolated patient sample, providing a relatively quick turnaround time needed for clinical practice. In addition, the simultaneous drawing of blood with the commencement of drug therapy will allow dosage adjustment on the basis of the CYP2D6 genotype to reduce the risk of adverse drug reactions.
Keywords: Humans; Cytochrome P-450 CYP2D6; DNA; Polymerase Chain Reaction; Sequence Analysis, DNA; Gene Frequency; Genotype; Phenotype
Rights: © Dustri-Verlag
RMID: 0020041143
DOI: 10.5414/CPP42719
Published version: http://www.ncbi.nlm.nih.gov/pubmed/15624288
Appears in Collections:Pharmacology publications

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