MDR1 gene polymorphisms and response to acute risperidone treatment

Kastelic, Matej; Koprivsek, Jure; Plesničar, Blanka Kores; Serretti, Alessandro; Mandelli, Laura; Locatelli, Igor; Grabnar, Iztok; Dolžan, Vita

doi:10.1016/j.pnpbp.2010.01.005

Cited by 39 publications

(24 citation statements)

References 49 publications

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“…Results from a recent study on 59 Slovenian patients with the first episode of schizophrenia, also treated with risperidone, indicate that heterozygous carriers of G2677T/A and C3435T polymorphism scored somewhat higher on scales measuring psychopathology and extrapyramidal side effects, but the difference was not significant and there was no tendency of gene-dose effect [27]. Interestingly, in our previous study we did find positive associations between ABCB1 2677T allele and 2677T/T genotype and better treatment response in female patients with schizophrenia who were treated with another atypical antipsychotic -olanzapine [28].…”

Section: Discussionmentioning

confidence: 96%

The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone

Jovanović

Božina

Lovrić

et al. 2010

Eur J Clin Pharmacol

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2 AbstractPurpose: To evaluate the role of cytochrome 450 2D6 (CYP2D6) and ABCB1 variants on plasma risperidone concentrations and treatment response in 83 drug naive patients with first episode of psychosis.Methods: All patients were treated with risperidone for 8 weeks. The CYP2D6 genotyping was performed by allele-specific PCR-RFLP (for *3,*4,*6) and long PCR (for duplications and *5), while real-time PCR method was used for ABCB1 G2677T/A and C3435T. Plasma concentrations of risperidone and 9-OH risperidone were measured by high-preformance liquid chromatography.Results: The number of patients with the CYP2D6 wild type (wt/wt), wt/mutation (mut) and mut/mut genotype was 43, 32 and 8, respectively. The number of patients with the ABCB1 2677G/G , G/T, T/T variants was 29, 42 and 12, respectively; those with the 3435C/C, C/T and T/T was 25, 37 and 21, respectively. The CYP2D6 genotype has strong effect on steady-state dose-corrected plasma levels of risperidone, its 9-OH metabolite and active moiety, while ABCB1 2677T/T and 3435T/T genotypes hold similarly strong effects on active moiety C/D. The CYP2D6 poor metabolizers had significantly higher levels of risperidone C/D and active moiety C/D, and lower levels of 9-OH risperidone C/D. The ABCB1 3435T allele and the ABCB1 2667T-3435T haplotype carriers were more frequent among subjects without extrapyramidal syndrome. Patients showed significant improvements in positive and general symptoms, but not in negative symptoms. These changes were not related to variations in genetic and drug concentration data.Conclusion: Our findings suggest that CYP2D6 and ABCB1 G2677T and C3435T might be useful determinants of risperidone plasma concentrations, but the clinical implications of these associations in relation to treatment response and side-effects remains unclear.

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Section: Discussionmentioning

confidence: 96%

The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone

Jovanović

Božina

Lovrić

et al. 2010

Eur J Clin Pharmacol

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“…55 There are also hints of an influence of MDR1 on weight gain 62 and metabolic disturbances caused by APs.…”

Section: Val(108/158)met Better Improvement Of Cognitive Function Wasmentioning

confidence: 99%

Pharmacogenetics of Antipsychotics

2014

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Objective: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors. Methods:We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses.Results: Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs. Conclusion:First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings. W W W La pharmacogénétique des antipsychotiquesObjectif : Au cours des dernières décennies, des efforts croissants ont été déployés dans des études visant à percer l'influence des facteurs génétiques sur le dosage des antipsychotiques (AP), la réponse au traitement, et la survenue d'effets indésirables. Ces études voulaient améliorer les soins cliniques en prédisant le résultat du traitement par AP, et en donnant lieu ainsi à des stratégies de traitement individualisées. Nous présentons les résultats les plus importants obtenus par des études tant de gènes candidats que d'association pangénomique, notamment les facteurs pharmacocinétiques et pharmacodynamiques. Méthodes :Nous avons passé en revue les études sur la pharmacogénétique de la réponse aux AP et des effets indésirables publiées dans PubMed jusqu'au début de 2012. Vu le nombre élevé d'études publiées, notre revue a mis l'accent sur les résultats qui ont été reproduits dans des études indépendantes ou qui sont soutenus par des méta-analyses.

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“…Некоторые авторы [56] не нашли ассоциации между полиморфизмом С3435Т MDR1 и развитием позд-ней дискинезии, другие исследователи [58] продемон-стрировали положительные результаты. Проводились также исследования относительно риска развития острых экстрапирамидных расстройств: в одних работах [59] была ЖУРНАЛ НЕВРОЛОГИИ И ПСИХИАТРИИ, 4,2015 ОБЗОРЫ установлена связь полиморфизмов MDR1 и экстрапира-мидных нарушений, в других [60] -был получен отрица-тельный результат. В целом необходимы дальнейшие ис-следования, чтобы оценить роль полиморфизмов MDR1 в возникновении побочных эффектов.…”

Section: генетическая изменчивость генов системы транспортеров гематоunclassified

Pharmacogenetic-based risk assessment of antipsychotic-induced extrapyramidal symptoms

Сосин

et al. 2015

Z. nevrol. psikhiatr. im. S.S. Korsakova

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MDR1 gene polymorphisms and response to acute risperidone treatment

Cited by 39 publications

References 49 publications

The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone

The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone

Pharmacogenetics of Antipsychotics

Pharmacogenetic-based risk assessment of antipsychotic-induced extrapyramidal symptoms

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