Resolution of a clinical AmpliChip CYP450 Test (TM) no call: discovery and characterization of novel CYP2D6*1 haplotypes
Por:
Gaedigk, A, Garcia-Ribera, C, Jeong, HE, Shin, JG, Hernandez-Sanchez, JT
Publicada:
1 jul 2014
Resumen:
A Han Chinese patient failed CYP2D6 genotype analysis with the AmpliChip CYP450 Test (TM). 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.
Filiaciones:
Gaedigk, A:
Childrens Mercy Hosp, Div Clin Pharmacol Toxicol & Therapeut Innovat, Kansas City, MO 64108 USA
Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA
Garcia-Ribera, C:
Univ Autonoma Barcelona, Dept Psychiat, Hosp St Pau, Inst Hosp Mar Invest Med, E-08193 Barcelona, Spain
Jeong, HE:
Inje Univ, Dept Pharmacol & Clin Pharmacol, Coll Med, Busan Paik Hosp, Pusan, South Korea
Shin, JG:
Inje Univ, Dept Pharmacol & Clin Pharmacol, Coll Med, Busan Paik Hosp, Pusan, South Korea
Hernandez-Sanchez, JT:
Lab Referencia Catalunya, Barcelona, Spain
Bronze
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