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.

Keywords::

• AmpliChip CYP450 Test™
• cytochrome CYP450
• CYP2D6
• CYP2D6*10
• genotyping
• pharmacogenetics

Acknowledgements

The authors are grateful to the technical assistance of A Riffel.

Financial & competing interests disclosure

This work was in part supported in part by grants A111218-11-PG02 from the National Project for Personalized Genomic Medicine, Korea Health 21 R&D Project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was in part supported in part by grants A111218-11-PG02 from the National Project for Personalized Genomic Medicine, Korea Health 21 R&D Project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.