Table 1. Assignment of Likely Phenotypes Based on Diplotypes.
| a. Assignment of CYP2D6 predicted phenotypes | |||
|---|---|---|---|
| Likely phenotype | Activity Score | Genotypes | Examples of CYP2D6diplotypes |
| Ultrarapid metabolizer (∼1-2% of patients)a | > 2.0 | An individual carrying duplications of functional alleles | *1/*1xN, *1/*2xN, *2/*2xNb |
| Extensive metabolizer (∼77-92% of patients) | 2.0-1.0c | An individual carrying two normal function alleles or two decreased function alleles or one normal function and one no function allele or one normal function and one decreased function allele | *1/*1, *1/*2, *1/*4, *1/*5, *1/*9, *1/*41, *2/*2,*41/*41 |
| Intermediate metabolizer (∼2-11% of patients) | 0.5 | An individual carrying one decreased function and one no function allele | *4/*10, *4/*41, *5/*9 |
| Poor metabolizers (∼5-10% of patients) | 0 | An individual carrying only no functional alleles | *3/*4, *4/*4, *5/*5, *5/*6 |
| b. Assignment of CYP2C19 predicted phenotypes | |||
| Likely phenotype | Genotypes | Examples of CYP2C19 diplotypes | |
| Ultrarapid metabolizer (∼5-30% of patients)d | An individual carrying two increased function alleles or one normal function allele and one increased function allele | *17/*17, *1/*17 | |
| Extensive metabolizer (∼35-50% of patients) | An individual carrying two normal function alleles | *1/*1 | |
| Intermediate metabolizer (∼18-45% of patients) | An individual carrying one normal function allele or one increased function allele and one no function allele | *1/*2, *1/*3, *2/*17e | |
| Poor metabolizer (∼2-15% of patients) | An individual carrying two no function alleles | *2/*2, *2/*3, *3/*3 | |
CYP2D6 metabolizer status frequencies are based on data from Caucasians and may differ from other ethnicities. See Supplemental Tables S3 and S6 note for information on the chances of observing specific diplotypes in different major race/ethnic groups.
Where xN represents the number of CYP2D6 gene copies. For individuals with CYP2D6 duplications or multiplications, see supplemental data for additional information on how to translate diplotypes into phenotypes.
Patients with an activity score of 1.0 may be classified as intermediate metabolizers by some reference laboratories.
CYP2C19 metabolizer status frequencies are based on average multi-ethnic frequency.
The predicted metabolizer phenotype for the *2/*17 genotypes is a provisional classification. The currently available evidence indicates that the CYP2C19*17 increased function allele is unable to completely compensate for the no function CYP2C19*2 (35). See Supplemental Materials for a more comprehensive list of predicted metabolizer phenotypes.