title: ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder.
abstract: Variability in antidepressant response is due to genetic and environmental factors. Among genetic factors, the ones controlling for availability of the drug at the target site are interesting candidates. Multidrug resistance 1 (ABCB1, MDR1) gene encodes a blood-brain barrier transporter P-glycoprotein that plays an important role in controlling the passage of substances between the blood and brain. In the present study, we therefore examined the possible association of 3 functional ABCB1 polymorphisms (C3435T: rs1045642, G2677T/A: rs2032582 and C1236T: rs1128503) with response to paroxetine in a Japanese major depression sample followed for 6 weeks. Analysis of covariance at week 6 with baseline scores included in the model as covariate showed significant association of the non-synonymous SNP G2677T/A with treatment response to paroxetine (p=0.011). Furthermore, the wild variants haplotype (3435C-2677G-1236T) resulted associated with poor response (p=0.006). To our best knowledge, this study is the first suggestion of a possible association of ABCB1 variants with SSRIs response.
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan. masaki.kato@unibo.it
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
authors.forename: Masataka
authors.initials: M
authors.lastname: Wakeno
authors.forename: Gaku
authors.initials: G
authors.lastname: Okugawa
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ikenaga
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hosoi
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Takekita
authors.forename: Laura
authors.initials: L
authors.lastname: Mandelli
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D019450:Genes, MDR / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C513055:ABCB1 protein, human; C493230:SLC6A4 protein, human