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ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine
Irina Piatkov1, Dorgival Caetano1, Yolinda Assur1
1University Clinic and Research Centre Blacktown, Western Sydney University, Western Sydney Local Health District, Blacktown, NSW, Australia.
Pharmacogenomics and Personalized Medicine
|September 19, 2017
Summary
Genetic variations in ATP-binding cassette (ABC) transporters influence clozapine (CZ) treatment outcomes. Specific single-nucleotide polymorphisms (SNPs) in ABCB1 and ABCC1 impact weight gain and cardiovascular markers in males, suggesting potential biomarkers for personalized schizophrenia treatment.
Area of Science:
- Pharmacogenetics
- Neuroscience
- Genetics
Background:
- Clozapine (CZ) is a highly effective antipsychotic for schizophrenia, but its efficacy and side effects can vary among patients.
- ATP-binding cassette (ABC) transporter proteins, including those encoded by ABCB1 and ABCC1, regulate drug distribution across biological membranes like the blood-brain barrier.
- Genetic variations (polymorphisms) in ABC transporters may influence individual responses to clozapine treatment.
Purpose of the Study:
- To investigate the impact of specific single-nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642) and ABCC1 (rs212090) on clozapine serum levels.
- To assess the influence of these SNPs on clinical outcomes, including changes in body mass index (BMI) and diastolic blood pressure during the first year of clozapine treatment.
- To explore the combined effect of these polymorphisms on clozapine and norclozapine serum concentrations.
Main Methods:
- Genotyping of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs).
- Measurement of clozapine (CZ) and norclozapine serum levels.
- Assessment of clinical outcomes, including body mass index (BMI) and diastolic blood pressure at baseline, 3 months, and 12 months of treatment.
Main Results:
- ABCB1 and ABCC1 polymorphisms significantly influenced baseline BMI and changes in BMI in males during clozapine treatment.
- These SNPs also affected diastolic blood pressure levels.
- The combined homozygote genotype for both ABCB1 and ABCC1 SNPs was associated with increased serum levels of clozapine and norclozapine.
Conclusions:
- Single-nucleotide polymorphisms in ABCB1 and ABCC1 may serve as potential biomarkers for predicting clozapine-induced weight gain and cardiovascular complications.
- These findings highlight the role of pharmacogenetics in understanding individual variability in clozapine response.
- Further research is warranted to guide personalized treatment decisions and preventive strategies for clozapine therapy.
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