Association of MDR1 C3435T polymorphism with bipolar disorder in patients treated with valproic acid

Turgut, Günfer; Kurt, Erhan; Şengül, Cem; Alataş, Gazi; Kursunluoglu, Raziye; Oral, Timuçin; Turgut, Sabahat; Herken, Hasan

doi:10.1007/s11033-007-9206-z

Cited by 17 publications

(7 citation statements)

References 31 publications

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“…For phenytoin, 3435CC seems to confer a lower C 0 [194] and an increased resistance rate [195]. For valproic acid, the available studies did not find a significant effect on kinetics [196] or the response rate [197]. One single study of lamotrigine in 222 Caucasian epilepsy patients reported that 1236CC and the CGC haplotype conferred a higher C 0 /D [198].…”

Section: Antiepileptic Drugsmentioning

confidence: 99%

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

et al. 2015

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ATP-binding cassette transporter B1 (ABCB1; P-glycoprotein; multidrug resistance protein 1) is an adenosine triphosphate (ATP)-dependent efflux transporter located in the plasma membrane of many different cell types. Numerous structurally unrelated compounds, including drugs and environmental toxins, have been identified as substrates. ABCB1 limits the absorption of xenobiotics from the gut lumen, protects sensitive tissues (e.g. the brain, fetus and testes) from xenobiotics and is involved in biliary and renal secretion of its substrates. In recent years, a large number of polymorphisms of the ABCB1 [ATP-binding cassette, sub-family B (MDR/TAP), member 1] gene have been described. The variants 1236C>T (rs1128503, p.G412G), 2677G>T/A (rs2032582, p.A893S/T) and 3435C>T (rs1045642, p.I1145I) occur at high allele frequencies and create a common haplotype; therefore, they have been most widely studied. This review provides an overview of clinical studies published between 2002 and March 2015. In summary, the effect of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small. Although polymorphisms and haplotypes of ABCB1 have been associated with alterations in drug disposition and drug response, including adverse events with various ABCB1 substrates in different ethnic populations, the results have been majorly conflicting, with limited clinical relevance. Future research activities are warranted, considering a deep-sequencing approach, as well as well-designed clinical studies with appropriate sample sizes to elucidate the impact of rare ABCB1 variants and their potential consequences for effect sizes.

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Section: Antiepileptic Drugsmentioning

confidence: 99%

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

et al. 2015

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“…While many anticonvulsant medications are MDR1 substrates and has been proposed as a potential mechanism of resistance to therapy, most studies have produced inconclusive results regarding the impact of MDR1 polymorphisms and a recent meta analysis of MDR1 C3435T genotype and resistance to anticonvulsant drugs failed to identify any significant association with resistance and MDR1 genotype [154]. In bipolar patients treated with valproic acid, no difference in serum valproic acid concentration was seen in patients exhibiting the C2335T polymorphism [155]. …”

Section: Pharmacogeneticsmentioning

confidence: 99%

Clinically Significant Psychotropic Drug-Drug Interactions in the Primary Care Setting

English

Dortch

Ereshefsky

et al. 2012

Curr Psychiatry Rep

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In recent years, the growing numbers of patients seeking care for a wide range of psychiatric illnesses in the primary care setting has resulted in an increase in the number of psychotropic medications prescribed. Along with the increased utilization of psychotropic medications, considerable variability is noted in the prescribing patterns of primary care providers and psychiatrists. Because psychiatric patients also suffer from a number of additional medical comorbidities, the increased utilization of psychotropic medications presents an elevated risk of clinically significant drug interactions in these patients. While life-threatening drug interactions are rare, clinically significant drug interactions impacting drug response or appearance of serious adverse drug reactions have been documented and can impact long-term outcomes. Additionally, the impact of genetic variability on the psychotropic drug’s pharmacodynamics and/or pharmacokinetics may further complicate drug therapy. Increased awareness of clinically relevant psychotropic drug interactions can aid clinicians to achieve optimal therapeutic outcomes in patients in the primary care setting.

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“…The DPC localizes to the sarcolemma, and its disruption is associated with various forms of muscular dystrophy. In brain, DTNB is found on neurons primarily in the cortex and hippocampus and it is expressed in postsynaptic membranes, suggesting a role in synaptic transmission [24]. Gaysina et al [25] found evidence for an association of the DTNBP1 (dystrobrevin-binding protein 1) gene with bipolar disorder, and Talbot et al [26] found a link between DTNBP1 and schizophrenia.…”

Section: Down-regulation Of Genes Associated With Bipolar Disordermentioning

confidence: 99%

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

Fatemi

Reutiman

Folsom

2009

Biochemical Society Transactions

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Bipolar disorder is a debilitating disorder of the brain with a lifetime prevalence of 1.0% for bipolar I, 1.1% for bipolar II disorder and 2.4-4.7% for subthreshold bipolar disorder. Medications, including lithium, have demonstrated efficacy in the treatment of bipolar disorder, but their molecular targets and mode of action are largely unknown. A few studies have begun to shed light on potential targets of lithium treatment that may be involved in lithium's therapeutic effect. We have recently conducted a microarray study of rat frontal cortex following chronic treatment (21 days) with lithium. Chronic treatment with lithium led to a significant (at least 1.5-fold) down-regulation of 151 genes and up-regulation of 57 genes. We discuss our results in the context of previous microarray studies involving lithium and gene-association studies to identify key genes associated with chronic lithium treatment. A number of genes associated with bipolar disorder, including Comt (catechol-O-methyltransferase), Vapa (vesicle-associated membrane protein-associated protein A), Dtnb (dystrobrevin beta) and Pkd1 (polycystic kidney disease 1), were significantly altered in our microarray dataset along with genes associated with synaptic transmission, apoptosis and transport among other functions.

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Association of MDR1 C3435T polymorphism with bipolar disorder in patients treated with valproic acid

Cited by 17 publications

References 31 publications

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

Clinically Significant Psychotropic Drug-Drug Interactions in the Primary Care Setting

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

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