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A monoamine oxidase B gene variant and short-term antidepressant treatment response
Authors:Tadić André  Rujescu Dan  Müller Matthias J  Kohnen Ralf  Stassen Hans H  Dahmen Norbert  Szegedi Armin
Affiliation:Department of Psychiatry, University of Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany. tadic@uni-mainz.de
Abstract:Genetic differences among patients suffering from Major Depression are likely to contribute to interindividual differences in medication treatment response. Thus, the identification of gene variants affecting drug response is needed in order to be able to predict response to psychopharmacological drugs. This study analyzed a possible association of the common A644G single nucleotide polymorphism (SNP) within intron 13 of the monoamine oxidase B (MAOB) gene with antidepressant treatment response. The study population consisted of n = 102 patients with major depression (criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSM-IV) participating in a randomized double-blind controlled clinical trial, conducted at 50 centers in Germany, comparing the efficacy of mirtazapine and paroxetine during 6 weeks of treatment. Overall, female patients homozygous for the A-allele had a significantly faster and more pronounced antidepressant treatment response than AG/GG-carriers. In paroxetine-treated females these differences remained statistically significant. In mirtazapine-treated females homozygous for the A-allele compared to AG/GG-carriers, HAMD-17 scores during the study period were constantly and markedly lower, but not statistically different. In males, we found no association between the MAOB A644G intron 13 SNP and antidepressant treatment response. Our data provide first suggestive evidence that the MAOB A644G SNP is involved in the outcome of treatment with mirtazapine or paroxetine in females with major depression. To confirm the role of the MAOB A644G gene variant in antidepressant treatment response, independent replications are needed. If replicated, the MAOB A644G polymorphism could be considered useful for prospective confirmatory pharmacogenetic trials in patients with major depression.
Keywords:  boldFont"  >5-HT, serotonin     boldFont"  >5-HTT, serotonin transporter     boldFont"  >ANOVA, analysis of variance     boldFont"  >bp, base-pair     boldFont"  >CEU-CEPH, Utah residents with ancestry from northern and western Europe     boldFont"  >CGI, Clinical Global Impressions Scale     boldFont"  >CI, 95%-confidence interval     boldFont"  >COMT, catechol-O-methyltransferase (gene)     boldFont"  >DA, dopamine     boldFont"  >DNA, Deoxyribonucleic acid     boldFont"  >DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition     boldFont"  >HAMD-17, Hamilton Rating Scale for Depression, 17-item version     boldFont"  >HTTLPR, Serotonin transporter gene-linked polymorphic region     boldFont"  >ITT, intention-to-treat     boldFont"  >LD, linkage disequilibrium     boldFont"  >MADRS, Montgomery–Asberg Depression Rating Scale     boldFont"  >MAOA, monoamine oxidase A (gene)     boldFont"  >MAO-A, monoamine oxidase A (enzyme)     boldFont"  >MAOB, monoamine oxidase B (gene)     boldFont"  >MAO-B, monoamine oxidase B (enzyme)     boldFont"  >MD, Major Depression     boldFont"  >MDE, major depressive episode     boldFont"  >M.I.N.I., Mini-International Neuropsychiatric Interview     boldFont"  >MMRM, mixed-effects model repeated measures     boldFont"  >mRNA, messenger Ribonucleic Acid     boldFont"  >n, number     boldFont"  >NE, Norepinephrine     boldFont"  >OR, Odds Ratio     boldFont"  >PCR, Polymerase chain reaction     boldFont"  >PD, Parkinson’s disease     boldFont"  >SNP, single nucleotide polymorphism     boldFont"  >SPSS, Statistical Package for the Social Sciences     boldFont"  >SSRI, selective serotonin reuptake inhibitor
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