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ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine
Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587196/ https://www.ncbi.nlm.nih.gov/pubmed/28919802 http://dx.doi.org/10.2147/PGPM.S142314 |
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author | Piatkov, Irina Caetano, Dorgival Assur, Yolinda Lau, Sue Lynn Jones, Trudi Boyages, Steven C McLean, Mark |
author_facet | Piatkov, Irina Caetano, Dorgival Assur, Yolinda Lau, Sue Lynn Jones, Trudi Boyages, Steven C McLean, Mark |
author_sort | Piatkov, Irina |
collection | PubMed |
description | Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood–brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment. These polymorphisms influenced baseline BMI in males (p=0.009 and 0.054, B1 and C1, respectively), changes in BMI in males after 3 (p=0.026, ABCB1) and 12 months (p=0.022, ABCC1) of CZ treatment, and level of diastolic pressure (p=0.002 and 0.051, respectively). The combination of ABCB1 + ABCC1 homozygote SNPs was associated with increased CZ and norclozapine serum levels (p=0.054 and 0.010, respectively). ABC transporter SNPs could be potential biomarkers for CZ-induced weight gain and cardiovascular complications. Further pharmacogenetic research is warranted to help clinicians with their treatment decision, including concomitant use of drugs and prevention of side effects. |
format | Online Article Text |
id | pubmed-5587196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55871962017-09-15 ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine Piatkov, Irina Caetano, Dorgival Assur, Yolinda Lau, Sue Lynn Jones, Trudi Boyages, Steven C McLean, Mark Pharmgenomics Pers Med Original Research Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood–brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment. These polymorphisms influenced baseline BMI in males (p=0.009 and 0.054, B1 and C1, respectively), changes in BMI in males after 3 (p=0.026, ABCB1) and 12 months (p=0.022, ABCC1) of CZ treatment, and level of diastolic pressure (p=0.002 and 0.051, respectively). The combination of ABCB1 + ABCC1 homozygote SNPs was associated with increased CZ and norclozapine serum levels (p=0.054 and 0.010, respectively). ABC transporter SNPs could be potential biomarkers for CZ-induced weight gain and cardiovascular complications. Further pharmacogenetic research is warranted to help clinicians with their treatment decision, including concomitant use of drugs and prevention of side effects. Dove Medical Press 2017-08-28 /pmc/articles/PMC5587196/ /pubmed/28919802 http://dx.doi.org/10.2147/PGPM.S142314 Text en © 2017 Piatkov et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Piatkov, Irina Caetano, Dorgival Assur, Yolinda Lau, Sue Lynn Jones, Trudi Boyages, Steven C McLean, Mark ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine |
title | ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine |
title_full | ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine |
title_fullStr | ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine |
title_full_unstemmed | ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine |
title_short | ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine |
title_sort | abcb1 and abcc1 single-nucleotide polymorphisms in patients treated with clozapine |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587196/ https://www.ncbi.nlm.nih.gov/pubmed/28919802 http://dx.doi.org/10.2147/PGPM.S142314 |
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