Resolution of a clinical AmpliChip CYP450 Test™ no call: discovery and characterization of novel CYP2D6*1 haplotypes

Pharmacogenomics. 2014 Jun;15(9):1175-84. doi: 10.2217/pgs.14.94.

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.

Keywords: AmpliChip CYP450 Test™; CYP2D6; CYP2D6*10; cytochrome CYP450; genotyping; pharmacogenetics.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alleles
  • Asian People / genetics
  • Cytochrome P-450 CYP2D6 / genetics*
  • DNA Copy Number Variations*
  • Female
  • Haplotypes
  • Humans
  • Pharmacogenetics / methods
  • Polymorphism, Single Nucleotide

Substances

  • Cytochrome P-450 CYP2D6