title: Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder: Sequencing Analysis of SLC6A4.
abstract: Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) are commonly used for treating major depression. Regretfully, significant heterogeneity exists regarding the benefits of SSRI/SNRI in individual cases. We previously reported that a polymorphism located in the serotonin transporter linked promoter region (5-HTT LPR) is associated with an interindividual difference in SSRI treatment efficacy. However, this explains only a small part of the variation of this complex phenotype. Other 5-HTT variants in the coding regions, 3' untranslated region (3' UTR), and introns adjacent to each exon could also contribute to treatment response. Therefore, we performed a sequencing analysis of the SLC6A4 gene (coding for 5-HTT) and investigated the association between variants detected in this study and the antidepressant response to SSRI/SNRI in 201 Japanese depressive patients. Seventeen novel mutations were identified by sequencing analysis. We found that the polymorphism G2563T (rs3813034) as a tag single-nucleotide polymorphism of IVS9 A-90G (rs140701), G2356T (rs1042173), and A3641C (rs7224199) is associated with interindividual variability of SSRI/SNRI efficacy at week 6, independent from clinical variables and effect of 5-HTT LPR (P < 0.001 by multiple regression analysis). This polymorphism could help determine individualized SSRI/SNRI treatments for depressive patients in combination with 5-HTT LPR.
authors.affiliation: From the *Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Hyogo; and †Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan; and ‡Department of Biomedical and Neuro Motor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Nonen
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Takekita
authors.forename: Masataka
authors.initials: M
authors.lastname: Wakeno
authors.forename: Shiho
authors.initials: S
authors.lastname: Sakai
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D017421:Sequence Analysis / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; C493230:SLC6A4 protein, human