1. Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder
- Author
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Yoshiteru Takekita, Toshihiko Kinoshita, Masataka Wakeno, Shinpei Nonen, Shiho Sakai, Masaki Kato, Alessandro Serretti, Nonen, Shinpei, Kato, Masaki, Takekita, Yoshiteru, Wakeno, Masataka, Sakai, Shiho, Serretti, Alessandro, and Kinoshita, Toshihiko
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,medicine.drug_class ,Serotonin and Noradrenaline Reuptake Inhibitor ,Polymorphism, Single Nucleotide ,Regression Analysi ,SLC6A4 ,03 medical and health sciences ,0302 clinical medicine ,SSRI/SNRI ,Internal medicine ,mental disorders ,Humans ,Medicine ,Pharmacology (medical) ,Serotonin and Noradrenaline Reuptake Inhibitors ,Polymorphism ,Serotonin Uptake Inhibitors ,Serotonin transporter ,Serotonin–norepinephrine reuptake inhibitor ,Serotonin Plasma Membrane Transport Proteins ,Individualized medicine ,Depressive Disorder, Major ,biology ,business.industry ,Middle Aged ,Serotonin Uptake Inhibitor ,Psychiatry and Mental health ,Treatment Outcome ,030104 developmental biology ,Endocrinology ,Norepinephrine transporter ,Sequence Analysi ,biology.protein ,Regression Analysis ,Antidepressant ,Female ,Serotonin ,business ,Reuptake inhibitor ,Sequence Analysis ,Selective Serotonin Reuptake Inhibitors ,Serotonin Plasma Membrane Transport Protein ,030217 neurology & neurosurgery ,Human - 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.
- Published
- 2016