CYP2D6 and CYP2C19 Genotyping
Genotyping of CYP2D6 and CYP2C19 variant alleles were performed using Taqman-based real-time PCR assays implemented and validated for routine pharmacogenetic testing at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway, described in detail elsewhere15,16.
The CYP2D6 pharmacogenetic panel included (i ) Null allelesCYP2D6*3 , *4 , *6 , (ii ) reduced-function (Red) alleles *9 , *10 and *41 , as well as (iii ) copy number analysis to identify CYP2D6*5 (whole gene deletion) allele and duplication of functional alleles (CYP2D6*1x3 ). The CYP2C19 pharmacogenetic panel included the non-functional allele CYP2C19*2. For the purpose of the present study, CYP2D6*1 and CYP2C19*1 were assigned to the alleles where no variant allele was detected with the abovementioned procedure. Since the assays could not discriminate between multiplications of functional, non-functional or reduced-functional variant allele combinations of CYP2D6 gene, patients with multiplied alleles of these combinations were not included. The patients were divided into the following CYP2D6 genotype-defined categories according to according to CPIC guidelines17: (i ) poor metabolizers (PMs;CYP2D6Null/Null ), (ii ) intermediate metabolizers (IM;CYP2D6Null/Red , and CYP2D6*1/Null andCYP2D6Red/Red ), (iii ) normal metabolizers (NMs;CYP2D6*1/Red , and CYP2D6*1/*1 ), and (iv ) ultrarapid metabolizers (UMs; CYP2D6*1x3 ). Patients were also categorized based on CYP2C19*2 carriers or noncarriers.