title: Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients.
abstract: 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].
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Nazan
authors.initials: N
authors.lastname: Yuce-Artun
authors.affiliation: School of Medicine, Psychiatry Department, Ankara University, Dikimevi, Ankara, Turkey.
authors.forename: Bora
authors.initials: B
authors.lastname: Baskak
authors.affiliation: School of Medicine, Psychiatry Department, Ankara University, Dikimevi, Ankara, Turkey.
authors.forename: Erguvan Tugba
authors.initials: ET
authors.lastname: Ozel-Kizil
authors.affiliation: School of Medicine, Psychiatry Department, Kirikkale University, Kirikkale, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Ozdemir
authors.affiliation: Faculty of Pharmacy, Department of Toxicology, Mersin University, Mersin, Turkey.
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Uckun
authors.affiliation: Faculty of Pharmacy, Department of Toxicology, Ankara University, Tandogan, Ankara, Turkey.
authors.forename: Halise
authors.initials: H
authors.lastname: Devrimci-Ozguven
authors.affiliation: Faculty of Pharmacy, Department of Toxicology, Ankara University, Tandogan, Ankara, Turkey. suzen@pharmacy.ankara.edu.tr.
authors.forename: Halit Sinan
authors.initials: HS
authors.lastname: Suzen
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000097:blood / Q000627:therapeutic use; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071184:Pharmacogenomic Variants / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020280:Sertraline / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; C585599:CYP2B6 protein, human; C045793:CYP2C19 protein, human; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D020280:Sertraline
keywords: CYP2B6; CYP2C19; Cytochrome P450; Pharmacogenetics; Sertraline
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