ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder.

Article Details

Citation

Copy to clipboard

Kato M, Fukuda T, Serretti A, Wakeno M, Okugawa G, Ikenaga Y, Hosoi Y, Takekita Y, Mandelli L, Azuma J, Kinoshita T

ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder.

Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):398-404. Epub 2007 Sep 15.

PubMed ID

17913323 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Citalopram	Multidrug resistance protein 1 Gene symbol: ABCB1 UniProt: P08183	---	(C;C) / (C;T)	C Allele (rs2032583)	Effect Directly Studied	Patients with this genotype have an increased likelihood of remission when using citalopram to treat major depressive disorder	Details
Venlafaxine	Multidrug resistance protein 1 Gene symbol: ABCB1 UniProt: P08183	---	(C;C) / (C;T)	C Allele (rs2032583)	Effect Directly Studied	Patients with this genotype have an increased likelihood of remission when using venlafaxine to treat major depressive disorder	Details
Amitriptyline	Multidrug resistance protein 1 Gene symbol: ABCB1 UniProt: P08183	---	(C;C) / (C;T)	C Allele (rs2032583)	Effect Directly Studied	Patients with this genotype have an increased likelihood of remission when using amitriptyline to treat major depressive disorder	Details
Paroxetine	Multidrug resistance protein 1 Gene symbol: ABCB1 UniProt: P08183	---	(C;C) / (C;T)	C Allele (rs2032583)	Effect Directly Studied	Patients with this genotype have an increased likelihood of remission when using paroxetine to treat major depressive disorder.	Details