MDR1 gene polymorphism: therapeutic response to paroxetine among patients with major depression.
The multidrug resistance transporter, P-glycoprotein (P-gp), encoded by polymorphic MDR1 (ABCB1) gene, is involved in efflux transport of several antidepressants and acts as a barrier to different exogenous noxa in the blood-brain barrier. MDR1 gene belongs to the best understood mediators of drug resistance. Different polymorphisms in MDR1 have been found to be connected with P-gp expression and function. The aims of the study were to investigate the potential influence of MDR1 polymorphisms, exon 26 C3435T and exon 21 G2677T/A, on treatment response to paroxetine (20 mg/day) in patients with major depression. To assess and evaluate therapeutic response to paroxetine, all patients were rated weekly using the HAMD-17 scale. Responders were defined as subjects with a decrease in HAMD scale by >or=50% at week 6 of treatment. The study population included 127 patients with major depression (diagnosed by Structured Clinical Interview for DSM-IV disorders). Our results indicated that MDR1 variants G2677T and C3435T are not associated with therapeutic response to paroxetine in patients with major depressive disorder. The associations between paroxetine and P-glycoprotein still need to be clarified.
Mihaljevic Peles
Alma
A
Department of Psychiatry, Zagreb University Hospital and University School of Medicine, Kispaticeva 12, 10 000 Zagreb, Croatia.
Bozina
Nada
N
Sagud
Marina
M
Rojnic Kuzman
Martina
M
Lovric
Mila
M
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D005189:False Positive Reactions; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000502:physiology; D017374:Paroxetine / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine