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    Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients
    (Springer, 2016) Yuce-Artun, Nazan; Baskak, Bora; Ozel-Kizil, Erguvan Tugba; Ozdemir, Hatice; Uckun, Zuhal; Devrimci-Ozguven, Halise; Suzen, Halit Sinan
    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.
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    The relationship between the serotonin 2A receptor gene-1438A/G and 102T/C polymorphisms and citalopram/sertraline-induced nausea in major depressed patients
    (Wiley, 2018) Oz, Merve Demirbugen; Uckun, Zuhal; Yuce-Artun, Nazan; Baskak, Bora; Ozdemir, Hatice; Ozel, Tugba Kizil; Suzen, H. Sinan
    Objective: The aim of the present study was to determine the relationship between the polymorphisms of -1438A/G and 102T/C in the 5-HT2A receptor (HTR2A) gene and nausea/vomiting as a side effect induced by sertraline (SERT) or citalopram (CIT) in patients with major depressive disorder. Methods: A total of 128 patients were enrolled, 63 patients received CIT, whereas 65 patients were treated with SERT. Nausea/vomiting were assessed with the UKU Side-effects Rating Scale at baseline and at the end of the second and fourth weeks. Polymerase chain reaction-restriction fragment length polymorphism technique was employed to determine genetic differences. Results: We have found that, in the patients treated with CIT, there was a nominally significant difference in the genotypic distribution associated with -1438A/G polymorphism between patients with and without nausea (X-2 = 6.15, p = 0.041). Moreover, logistic regression analysis revealed a significant association between nausea/vomiting as a side effect and -1438A/G polymorphism. That is, patients with the G allele were at a higher risk for developing nausea/vomiting (p = 0.044, odds ratio = 2.213). The 102T/C polymorphism in the HTR2A gene had no significant effect on the nausea/vomiting as a side effect among participants treated with either CIT or SERT. Conclusion: The present study suggests the association of the HTR2A gene -1438A/G polymorphism with nausea/vomiting as a side effect related to CIT treatment.