Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

are compound heterozygous for these polymorphisms are poor metabolizers. The following information
outlines the relationship between the polymorphisms detected in the CYP2D6 genotyping assay and the
effect on the activity of the enzyme produced by that allele: Allele Designation Nucleotide Change Effect
on CYP2D6 mRNA or Protein Effect and Phenotype *1 No polymorphisms detected Normal mRNA and
protein Normal activity; predicted extensive metabolizer status for tamoxifen *2A -1584C->G Increased
transcription *3 2549A->del Nonsense mutation No activity; predicted poor metabolizer status for
tamoxifen. *4 1846G->A mRNA splicing *5 gene deletion Entire gene deleted *6 1707T->del Nonsense
mutation *7 2935A->C Missense mutation *8 1758G->T Stop codon *11 883G->C mRNA splicing *12
124G->A Missense mutation *14A 100C->T 1758G->A Missense mutation *15 138insT Nonsense
mutation *2 2850C->T Missense mutation Activity with tamoxifen has not been determined; metabolizer
status for tamoxifen unknown. *9 2613AGA>del Lysine282 deletion *10 100C->T Missense mutation
*14B 1758G->A Missense mutation *17 1023C->T Missense mutation *41 2988G->A mRNA splicing
Gene duplications Whole gene duplication Depends on the allele duplicated. Allele duplication may result
in no change in activity (duplication of deficient alleles) or potentially increase the metabolism of
tamoxifen (ultrarapid metabolism). A complicating factor in correlating CYP2D6 genotype with
phenotype is that many drugs or their metabolites are inhibitors of CYP2D6 catalytic activity. For
example, many antidepressants, including some of the tricyclic antidepressants and some of the selective
serotonin reuptake inhibitors, especially fluoxetine and paroxetine, are particularly inhibitory to CYP2D6
activity. Other drugs that inhibit CYP2D6 activity include some cardioactive drugs (eg, quinidine and
amiodarone), some drugs of abuse (eg, cocaine), methadone, many histamine H1 receptor antagonists (eg,
cimetidine), celecoxib, and ritonavir. Comedication with tamoxifen and inhibitory drugs may produce a
CYP2D6 poor metabolizer phenotype, even though the patient has a CYP2D6 genotype consistent with
intermediate or extensive metabolism. Consequently, it is important to interpret the results of CYP2D6
genotype testing in the context of coadministered drugs. Because antidepressants are often prescribed to
alleviate the hot flashes that accompany tamoxifen therapy, it is particularly important to utilize an
antidepressant that does not compromise CYP2D6 activity, which could reduce tamoxifen's efficacy.
Useful For: Determining the CYP2D6 genotype of patients considered for tamoxifen chemotherapy
Interpretation: An interpretive report will be provided that includes assay information, genotype,
and an interpretation indicating the patient's ability to activate tamoxifen to endoxifen. Based on the test
sensitivity and currently available CYP2D6 polymorphism carrier frequencies, persons of Caucasian
descent who tested negative for the above polymorphisms would be estimated to have a