Resolution of a clinical AmpliChip CYP450 Test™ no call: discovery and characterization of novel CYP2D61 haplotypes

• Published in: Pharmacogenomics Vol. 15; no. 9; pp. 1175 - 1184
• Main Authors: Gaedigk, Andrea, Garcia-Ribera, Carles, Jeong, Hye-Eun, Shin, Jae-Gook, Hernandez-Sanchez, Juanjo, Hernandez-Sanchez, Juanjo T
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.07.2014
• Subjects: Aged, 80 and over; Alleles; Asian Continental Ancestry Group - genetics; Cytochrome P-450; Cytochrome P-450 CYP2D6 - genetics; DNA Copy Number Variations; Female; Genetic screening; Haplotypes; Humans; Identification and classification; Pharmacogenetics - methods; Polymorphism, Single Nucleotide; AmpliChip CYP450 Test; cytochrome CYP450; CYP2D610; CYP2D6; pharmacogenetics; genotyping
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/PGS.14.94

A Han Chinese patient failed CYP2D6 genotype analysis with the AmpliChip CYP450 Test™. The CYP2D6 gene locus of the patient and her son were extensively genotyped including copy number variation and gene resequencing. Two SNPs were discovered on the patient's CYP2D6*1 allele, -498C>A and 1661G>C, while the son's CYP2D6*1 allele had -498C>A only. AmpliChip failure was attributed to the presence of a CYP2D6*1 allele carrying the 1661G>C SNP. Functional analyses of -498C>A did not reveal altered activity in vitro or in vivo suggesting that both novel CYP2D6*1 subvariants are functional. The implementation of pharmacogenetics-guided drug therapy relies on accurate clinical-grade genotype analysis. Although the AmpliChip is a reliable platform, numerous allelic (sub)variants and gene arrangements are not detected or may trigger no calls. While such cases may be rare, the clinical/genetic testing community must be aware of the challenges of CYP2D6 testing on the AmpliChip platform and implications regarding accuracy of test results.