Allele Drop Out Conferred by a Frequent CYP2D6 Genetic Variation For Commonly Used CYP2D6*3 Genotyping Assays
| Autor: | George P Patrinos, Davide Antonio Civello, Selma M. Soyal, Charity Nofziger, Silvia Dossena, Giada Scantamburlo, Simone Vanoni, Wolfgang Patsch, Konstantina Tziolia, Emanuele Bernardinelli, Markus Paulmichl, Michaela Zopf |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
DNA Copy Number Variations Genotype Genotyping Techniques Physiology Biology digestive system lcsh:Physiology Cohort Studies lcsh:Biochemistry 03 medical and health sciences symbols.namesake Gene Frequency Genetic variation Humans lcsh:QD415-436 Copy-number variation Allele skin and connective tissue diseases Allele frequency Genotyping Alleles Sanger sequencing Genetics lcsh:QP1-981 Precision medicine Discriminant Analysis Pyrosequencing DNA Sequence Analysis DNA 3. Good health Phenotype 030104 developmental biology Cytochrome P-450 CYP2D6 Haplotypes Pharmacogenetics symbols Pharmacogenomics |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 43, Iss 6, Pp 2297-2309 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aim: Accurate genotyping of CYP2D6 is challenging due to its inherent genetic variation, copy number variation (duplications and deletions) and hybrid formation with highly homologous pseudogenes. Because a relatively high percentage (∼25%) of clinically prescribed drugs are substrates for this enzyme, accurate determination of its genotype for phenotype prediction is essential. Methods: A cohort of 365 patient samples was genotyped for CYP2D6 using Sanger sequencing (as the gold standard), hydrolysis probe assays or pyrosequencing. Results: A discrepant result between the three genotyping methods for the loss of function CYP2D6*3 (g.2549delA, rs35742686) genetic variant was found in one of the samples. This sample also contained the CYP2D6 g.2470T>C (rs17002852) variation, which had an allele frequency of 2.47% in our cohort. Redesign of the CYP2D6*3 pyrosequencing and hydrolysis probe assays to avoid CYP2D6 g.2470 corrected the anomaly. Conclusion: To evidence allele drop out and increase the accuracy of genotyping, intra-patient validation of the same genetic variation with at least two separate methods should be considered. |
| Databáze: | OpenAIRE |
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