Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients
- 726 Downloads
Background Genetic polymorphisms in CYP2B6 and CYP2C19 may cause variability in the metabolism of sertraline, a widely used antidepressant in major depressive disorder treatment. Objective This study investigates the impact of CYP2B6*4 (785A > G), CYP2B6*9 (516G > T), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (685G > A), CYP2C19*17 (−3402C > T) polymorphisms on plasma concentrations of sertraline and N-desmethyl sertraline in major depression patients treated with sertraline [n = 50]. Setting Participants were patients who admitted to an adult psychiatry outpatient unit at a university hospital. These were DSM-IV major depression diagnosed patients with a stable sertraline medication regimen [for at least one month]. Methods CYP2B6*4 (rs 2279343; 785A > G), CYP2B6*9 (516G > T; rs 3745274), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (rs 4244285; 685G > A), CYP2C19*17 (rs 11188072; −3402C > T), polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Plasma concentrations were measured by high-performance liquid chromatography in patients treated with SERT. Main outcome measure The distribution of CYP2B6*4, *6, *9 and CYP2C19*2, *17 among patient group and the association between genotype and sertraline metabolism. Results Sertraline, N-desmethyl sertraline, N-desmethyl sertraline/sertraline and dose-adjusted plasma concentrations were statistically compared between individuals with wild-type and variant alleles both for CYP2B6 and CYP2C19 enzymes. The mean N-desmethyl sertraline/sertraline value, was significantly lower in all subgroups with *6 and *9 variant alleles (p < 0.05). Sertraline/C values were significantly higher (p < 0.05) and N-desmethyl sertraline/C values were lower in all subgroups with *6 and *9 variant alleles compared to wild-type subgroup. Conclusion CYP2B6*6 and *9 variant alleles had a significant decreasing effect on sertraline metabolism in major depression patients which might result as variations in sertraline therapy.
KeywordsCYP2B6 CYP2C19 Cytochrome P450 Sertraline Pharmacogenetics
We acknowledge nurses for the skilled assistance during blood collection in the psychiatry departments.
This work was supported by The Scientific and Technological Research Council of Turkey under Project 109S147.
Conflicts of interest
The authors declare that they have no conflict of interest.
- 20.Reis M, Aberg-Wistedt A, Agren H, Höglund P, Akerblad AC, Bengtsson F. Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression. Hum Psychopharmacol. 2004;19:283–91.CrossRefPubMedGoogle Scholar
- 30.First MB, Spitzer RL, Gibbon M, et al. Structured clinical interview for DSM-IV clinical version [SCID-I/CV]. American Psychiatric Pres: Washington DC; 1997.Google Scholar
- 33.Yuce-Artun N, Ozel Kizil ET, Baskak B, Devrimci Ozguven H, Duydu Y, Suzen HS. Determination of sertraline and its metabolite by high-pressure liquid chromatography in plasma. Rev Roum Chim. 2015;60(5–6):543–8.Google Scholar
- 38.Hofmann MH, Blievernicht JK, Klien K, Saussele T, Schaeffeler E, Schwab M, et al. Aberrant splicing caused by single nucleotide polymorphism c.516G > T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CY2B6 in liver. J Pharmacol Exp Ther. 2008;325:284–92.CrossRefPubMedGoogle Scholar