ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder |
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Authors: | Kato Masaki Fukuda Tsuyoshi Serretti Alessandro Wakeno Masataka Okugawa Gaku Ikenaga Yuka Hosoi Yuka Takekita Yoshiteru Mandelli Laura Azuma Junichi Kinoshita Toshihiko |
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Affiliation: | Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan. masaki.kato@unibo.it |
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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. |
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Keywords: | 5-HTTLPR, Serotonin Transporter Gene Promoter Polymorphism HAM-D, Hamilton Rating Scale for Depression ABCB1, Multidrug resistance 1 P-gp, P-glycoprotein SCID-I, The Structured Clinical Interview for DSM-IV Axis I Disorders SNPs, single nucleotide polymorphisms |
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