title: Resolution of a clinical AmpliChip CYP450 Test™ no call: discovery and characterization of novel CYP2D6*1 haplotypes.
abstract: 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.
authors.affiliation: Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Hospital, 2401 Gilham Road, Kansas City, MO 64108, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gaedigk
authors.forename: Carles
authors.initials: C
authors.lastname: Garcia-Ribera
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Jeong
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
authors.forename: Juanjo
authors.initials: J
authors.lastname: Hernandez-Sanchez
authors.forename: Juanjo T
authors.initials: JT
authors.lastname: Hernandez-Sanchez
mesh_terms: D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D006239:Haplotypes; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide
chemical_list: D019389:Cytochrome P-450 CYP2D6
keywords: AmpliChip CYP450 Test™; CYP2D6; CYP2D6*10; cytochrome CYP450; genotyping; pharmacogenetics