Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein).

Department of Genetics, Stanford University Medical Center, Stanford, California 94305-5120, USA.
Pharmacogenetics and Genomics (Impact Factor: 3.45). 03/2011; 21(3):152-61. DOI: 10.1097/FPC.0b013e3283385a1c
Source: PubMed
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    ABSTRACT: Those suicide attempters that choose violent methods dramatically diminish the possibility of survival. Completed suicide using violent means, which is common among first-time suicide attempters, was recently found to be more likely among T allele carriers in the three most common ABCB1 SNPs, encoding for P-gp. Thus, this study examined, for the first time, whether these ABCB1 SNPs were associated with the use of violent means among survivors of a suicide attempt. Suicide attempters (n = 578, 87.4% women; of whom 16.6% committed a violent intent) were genotyped for exonic SNPs in the ABCB1 (C1236T, G2677T/A, C3435T). The relations of the three genotypes and of the TTT haplotype with the use of a violent suicide method were evaluated separately. The impact of confounds on these variables was controlled. A higher frequency (p = 0.02) of suicide attempters using violent methods was found among those carrying the ABCB1 haplotype (1236TT-2677TT-3435TT). Since gender and number of previous suicide attempts were identified as confounds, the relation was tested in the subset of women who were first-time attempters or second- and more-time attempters. The ABCB1 haplotype increased the risk more than three times in those women attempting a violent suicide for the first time (OR = 3.6; CI95%: 1.08-12.09; p = 0.04). The ABCB1 haplotype (1236TT-2677TT-3435TT) was related to the use of a violent suicide attempt method. Genotyping for these three ABCB1 SNPs may be helpful to detect people at risk of first suicide intents using violent methods. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Journal of Psychiatric Research 12/2014; 61. DOI:10.1016/j.jpsychires.2014.12.005 · 4.09 Impact Factor
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    ABSTRACT: The efflux pump P-glycoprotein (P-gp), a gene product of the ABCB1 gene, plays a pivotal role in the transfer of various molecules across the blood-brain barrier. P-gp protects the brain by selectively extruding its substrates, including certain antidepressive drugs, thereby limiting their uptake into the brain. Uhr et al. [2008] first showed that ABCB1 variants predicted the remission to antidepressants with P-gp substrate properties in patients suffering from major depression (MD). Other studies investigating the influence of ABCB1 polymorphisms on antidepressant treatment response produced inconclusive results. In this meta-analysis, we systematically summarized 16 pharmacogenetic studies focused on the association of ABCB1 variants and antidepressant treatment outcome in patients with MD (overall n = 2695). We investigated the association of treatment outcome and six ABCB1 single nucleotide polymorphisms (SNPs): rs2032583, rs2235015, rs2235040, rs1045642, rs2032582, rs1128503. We stratified for admission status, ethnicity, and prescription of concomitant medication. SNP rs2032583 showed a nominally significant association across all studies (P = 0.035, SNP was studied in a total of 2,037 patients) and a significant Bonferroni-corrected association among inpatients (P = 1.5 × 10(-05) , n = 485). Also SNP rs2235015 was significantly associated with antidepressant treatment outcome withstanding Bonferroni correction (P = 3.0 × 10(-04) ) among inpatients in a smaller subsample (n = 195). There were no significant associations of the other SNPs tested with antidepressant treatment outcome. Future pharmacogenetic association studies should focus on the role of the ABCB1 SNP rs2032583 in antidepressant outcome prediction. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2015; DOI:10.1002/ajmg.b.32309 · 3.27 Impact Factor
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    ABSTRACT: Introduction: Multiple strategies exist for the pharmacological treatment of schizophrenia and related disorders. In the last 20 years, several 'new' compounds have been introduced, called 'atypical antipsychotics', which have higher efficacy and better tolerability than first-generation neuroleptics. Among them, ziprasidone (ZPR) is currently finding widespread use, and it has also been shown to be active as an augmenter in bipolar disorder therapy. Areas covered: This review aims to provide the latest information on ZPR, an 'atypical' agent for the pharmacological therapy of schizophrenia and bipolar disorder. A literature search has been carried out with the keywords 'ziprasidone', 'schizophrenia', 'psychosis', 'bipolar', 'pharmacokinetics' and 'clinical trials'. In this process, particular attention has been paid to the drug pharmacokinetic characteristics and its safety in clinical use. Expert opinion: ZPR shares most advantages and disadvantages with other atypical antipsychotics. However, it can be useful for its low tendency to cause metabolic syndrome and hyperprolactinaemia, especially in patients suffering from excess weight, hyperlipidaemia, diabetes or who have suffered from hyperprolactinaemia when using other antipsychotics. However, there are serious doubts as to whether ZPR should be administered to patients suffering from arrhythmias or QTc prolongation, and even more for administration to bipolar patients undergoing polypharmacy with antidepressants.
    Expert Opinion on Drug Metabolism &amp Toxicology 12/2014; 11(1):1-26. DOI:10.1517/17425255.2015.991713 · 2.93 Impact Factor

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