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CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions.


Pharmacogenomics. 2013 Jul;14(10):1191-201


Authors: Kuo HW, Liu SC, Tsou HH, Liu SW, Lin KM, Lu SC, Hsiao MC, Hsiao CF, Liu CY, Chen CH, Lu ML, Shen WW, Tang HS, Liu SI, Chang LH, Wu HY, Chang YS, Yeh TK, Chen ACh, Liu YL


Abstract

Aim: The liver CYP1A2 enzyme may metabolize antidepressant escitalopram (S-CIT) to S-desmethylcitalopram (S-DCIT) and S-didesmethylcitalopram (S-DDCIT). This study tested whether genetic polymorphisms in the CYP1A2 gene are associated with the treatment responses to S-CIT. Materials & methods: Ten SNPs in CYP1A2 were selected and genotyped in 158 patients under S-CIT treatment. The serum levels of S-CIT and its metabolites were measured by HPLC. Results:CYP1A2 SNPs rs2069521, rs2069526, rs4646425 and rs4646427 are significantly associated with the metabolic ratios of S-DDCIT/S-DCIT (p = 0.002, 0.018, 0.008 and 0.004, respectively) at week 2 of treatment. Carriers of the allele types associated with higher S-DDCIT/S-DCIT ratios had more severe side effects. Conclusion: These results suggest that genetic variants in CYP1A2 may be indicators for S-CIT metabolism and that the fast metabolizers may experience more severe adverse reactions in the early stages of S-CIT treatment. Original submitted 27 December 2012; Revision submitted 15 May 2013.

PMID: 23859573 [PubMed - in process]