Posted by Admin (@hinadmin) · Thu, Mar 13 at 2:48pm CDT
Citalopram and Escitalopram Plasma Drug and Metabolite Concentrations: Genome-Wide Associations
A recently published article in the area of Pharmacogenomics set out to identify genetic factors in Citalopram (CT) and escitalopram (S-CT), which are among the most widely prescribed serotonin reuptake inhibitors (SSRIs) used to treat Major Depressive Disorder (MDD), that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT. The GWAS was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy) and SNPs were modeled as additive allelic effects.
Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, p = 4.07E-09) and with S-DDCT concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1058172, p = 2.0E-16), supporting the important role of these CYP enzymes in citalopram biotransformation. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation. The results of the GWAS performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these SSRIs.