Investigation of polymorphism in the MDR1 gene and antidepressant-induced mania

Introduction: Pharmacogenetic factors may explain some of the interindividual variability of response to antidepressants in depressed patients. We focused on P-glycoprotein (P-GP), whose expression depends on a functional polymorphism of the ABCB1 gene (C3435T variants: dbSNP: rs1045642), the 3435CC genotype being linked to a high level of P-GP expression. Acting as an efflux pump at the blood-brain barrier, P-GP reduces the intracellular penetration of many drugs. Little is known about the interaction between P-GP and response to antidepressants. The objective of this study is to assess whether the response to antidepressants in depression differs in patients with the 3435CC genotype as compared to patients with the 3435CT and 3435TT genotypes. Methods: 117 in-patients with a major depressive episode requiring a new antidepressant treatment were enrolled in this prospective naturalistic 4-week study. Response to antidepressants was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, the Clinician Global Impression Improvement and Therapeutic Index, and weight change. ABCB1 genotyping was performed using the Taqman method. Clinical assessment was performed blind from genotypes. Results: We failed to show any significant effect of the ABCB1 polymorphism in position 3435 on antidepressant efficacy or tolerance. Discussion: While some in vitro studies showed an influence of P-GP on cerebral concentrations of antidepressants, our results do not support the hypothesis that the C3435T polymorphism is involved in therapeutic response and safety of antidepressants in naturalistic clinical conditions, confirming results of previous studies on efficacy. Nonetheless, some methodological limitations may explain our negative results.

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“…It is also consistent with a study showing no significant association between antidepressant induced-mania and C3435T polymorphism [26] .…”

Section: Discussionsupporting

confidence: 92%

Antidepressants and ABCB1 Gene C3435T Functional Polymorphism: A Naturalistic Study

Gressier

Verstuyft

et al. 2010

Neuropsychobiology

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“…The second study 75 examined the association in 26 patients with antidepressant-induced mania (compared with 29 patients with no such history) with the 3435C4T polymorphism. All patients were in HWE and no association was found between genotype or allele frequency and the occurrence of mania.…”

Section: Antidepressantsmentioning

confidence: 99%

ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research

et al. 2006

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The product of the ABCB1 gene, P-glycoprotein (PGP), is a transmembrane active efflux pump for a variety of drugs. It is a putative mechanism of multidrug resistance in a range of diseases. It is postulated that ABCB1 polymorphisms contribute to variability in PGP function, and that therefore multidrug resistance is, at least in part, genetically determined. However, studies of ABCB1 genotype or haplotype and PGP expression, activity or drug response have produced inconsistent results. This critical review of ABCB1 genotype and PGP function, including mRNA expression, PGP-substrate drug pharmacokinetics and drug response, highlights methodological limitations of existing studies, including inadequate power, potential confounding by co-morbidity and co-medication, multiple testing, poor definition of disease phenotype and outcomes, and analysis of multiple drugs that might not be PGP substrates. We have produced recommendations for future research that will aid clarification of the association between ABCB1 genotypes and factors related to PGP activity.

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“…Bcl-2, the most striking in many genes involved in apoptosis, is related to the incidence and development of tumours and sensitivity to chemotherapeutic drugs (7). Drug resistance of tumour cells, the major cause of failure of chemotherapy, involves a number of factors, among which apoptosis is at the intersection of a variety of drug-resistant pathways (8). Thus, induction of apoptosis has been one of the hotspots of the treatment of cancer (9).…”

Section: Introductionmentioning

confidence: 99%

The Effect and Mechanisms of Proliferative Inhibition of Crocin on Human Leukaemia Jurkat Cells

Sun

Wang

et al. 2016

West Indian Med J

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Investigation of polymorphism in the MDR1 gene and antidepressant-induced mania

Cited by 41 publications

References 23 publications

Antidepressants and ABCB1 Gene C3435T Functional Polymorphism: A Naturalistic Study

Antidepressants and ABCB1 Gene C3435T Functional Polymorphism: A Naturalistic Study

ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research

The Effect and Mechanisms of Proliferative Inhibition of Crocin on Human Leukaemia Jurkat Cells

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