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Naturalistic pharmacogenetic study of treatment resistance to typical neuroleptics in European–Brazilian schizophrenics
- Source :
- Pharmacogenetics and Genomics. 18:599-609
- Publication Year :
- 2008
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2008.
-
Abstract
- This study aimed to explore the influence of variation in DRD2, DRD3, CYP2D6, CYP3A4, and CYP3A5 genes on treatment resistance to typical neuroleptics in a Brazilian sample of patients with schizophrenia.One polymorphism at DRD2 gene, five at DRD3, 24 at CYP2D6, nine at CYP3A4 gene, and one at CYP3A5 gene were genotyped in a sample of 186 patients with schizophrenia.From the nine studied CYP3A4 single nucleotide polymorphisms, only the -392AG was polymorphic, and significant associations were observed between this single nucleotide polymorphism and efficacy of neuroleptic treatment. Homozygous individuals for the -392A variant [P=0.014, odds ratio (OR)=3.32] were more frequent in the treatment-resistant group, compared with carriers of one copy of the -392G variant. The CYP3A5 low expressor genotype (CYP3A5*3/CYP3A5*3) was found to be associated with refractoriness to neuroleptic treatment (P=0.003, OR=3.16). Among the haplotypes observed in DRD3 gene, the T/A/G/A/C haplotype showed an association with refractoriness to neuroleptics (chi=5.342, P=0.021, OR=1.75). This association showed that carriers of one copy of this haplotype presented intermediate values between noncarriers and homozygous individuals for the haplotype. No association was observed with polymorphisms in DRD2 and CYP2D6 genes. Multiple logistic regression analyses showed that the number of copies of DRD3 T/A/G/A/C haplotype and CYP3A5 low expressor genotype were predictors of refractoriness to neuroleptic after controlling for selected risk factors. CYP3A5*3 individuals carrying at least one copy of the T/A/G/A/C haplotype showed a higher risk to be refractory to neuroleptics than CYP3A5*3 homozygotes+non-T/A/G/A/C carriers (chi=5.533, P=0.019, OR=2.32, 95% confidence interval=1.08-5.02). No significant associations were observed with DRD2 and CYP2D6 polymorphisms.Our results suggest a role for CYP3A5 and DRD3 gene variants on refractoriness to neuroleptic treatment in Brazilians with schizophrenia.
- Subjects :
- Adult
Male
Psychosis
CYP2D6
medicine.medical_specialty
Adolescent
Genotype
Drug Resistance
Biology
Polymorphism, Single Nucleotide
digestive system
Pharmacogenetic Study
White People
Cytochrome P-450 Enzyme System
Gene Frequency
Polymorphism (computer science)
Genetics
medicine
Cytochrome P-450 CYP3A
Humans
General Pharmacology, Toxicology and Pharmaceutics
Treatment resistance
skin and connective tissue diseases
CYP3A5
Psychiatry
Molecular Biology
Genetics (clinical)
Aged
Receptors, Dopamine D2
Receptors, Dopamine D3
Middle Aged
medicine.disease
Cytochrome P-450 CYP2D6
Pharmacogenetics
Schizophrenia
Molecular Medicine
Female
Brazil
Antipsychotic Agents
Subjects
Details
- ISSN :
- 17446872
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Pharmacogenetics and Genomics
- Accession number :
- edsair.doi.dedup.....c22ed6ea15fb25e7c4b10e5fe0e6bde7