Association between dopamine receptor gene polymorphisms and effects of risperidone treatment: A systematic review and meta‐analysis

Ma, Lei; Zhang, Xiaodan; Xiang, Qian; Zhou, Shuang; Zhao, Nan; Xie, Qiufen; Zhao, Xia; Zhou, Ying; Chen, Yimin

doi:10.1111/bcpt.13111

Cited by 19 publications

(23 citation statements)

References 29 publications

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“…Recently, consistently with our results, a meta-analysis reported an association between A allele and a significant greater improvement with risperidone treatment. 44 Finally, we did not replicate the association between Taq1A, C939T, and C376G and the AP response in schizophrenia patients.…”

Section: Discussionmentioning

confidence: 62%

“…Similarly, Hwang et al 47 found a gene × gene interaction between the Gly allele/ DRD3 and the G allele/ DRD1 in ultraresistant patients with schizophrenia. Ebstein et al, 48 Lane et al, 21 and Ma et al, 44 in three different ethnic groups, established an association between response to conventional APs and the Ser allele. However, other studies have reported an association between the response and the Gly allele.…”

Section: Discussionmentioning

confidence: 98%

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Association study between COMT, DRD2, and DRD3 gene variants and antipsychotic treatment response in Mexican patients with schizophrenia

Escamilla¹,

Camarena²,

Saracco-Álvarez³

et al. 2018

NDT

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PurposeThe efficacy of schizophrenia treatments using antipsychotics (APs) has long been established, but the benefit obtained by several patients using conventional APs (typical or atypical) has not been enough. Currently, the genetic study of the primary mechanisms of action of the APs has been focused on the dopaminergic pathways. The objective of this study was to determine if the response phenotypes (responder, resistance to treatment, and ultra-resistance to treatment groups) are associated with six single-nucleotide polymorphisms: COMT (Val158Met), DRD2 (A-241G, C376G, C939T, Taq1A), and DRD3 (Ser9Gly).Patients and methodsWe classified the patients through a retrospective/prospective methodology to define response phenotypes.ResultsCOMT/Val158Met and DRD3/Ser9Gly were associated with the responder group (P<0.05). The single-nucleotide polymorphism A-241G of DRD2 gene was related with the resistant-to-treatment group (P<0.001). Finally, Met/Met of COMT and Ser/Gly of DRD3 genes showed a predictive effect associated with the resistant-to-treatment phenotype.ConclusionFurther analyses should be performed to validate these genetic markers as mediators for the response to APs.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 98%

Association study between COMT, DRD2, and DRD3 gene variants and antipsychotic treatment response in Mexican patients with schizophrenia

Escamilla¹,

Camarena²,

Saracco-Álvarez³

et al. 2018

NDT

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“…Indeed, when the haplotype block CCGCCGTT (rs6277-rs1076560-rs2283265-rs2734833-rs2075652-rs1079596-rs4436578-rs11214607) was considered, phenotypic associations of the block were found to be associated with heroin dependence behavior [ 26 ]. As a clinically actionable target, a metanalysis has supported the hypothesis that rs6277 potentially alters response to risperidone treatment of schizophrenia [ 31 ], possibly doing so through altered expression, although a definitive conclusion could not be found at this time.…”

Section: Discussionmentioning

confidence: 99%

Expression of Dopamine-Related Genes in Four Human Brain Regions

Stanfill

Cao

2020

Brain Sciences

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A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions.

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“…В поле зрения учёных преимущественно попадают рецепторы дофамина 2, 3 и 4-го типов, поскольку в основном они связаны с фармакодинамикой антипсихотиков [3]. Существуют несколько мета-анализов, подтверждающих связь между носительством полиморфизмов гена DRD2 и недостаточным ответом на антипсихотики [8,9]. Полиморфизм DRD3 rs6280 также демонстрировал ассоциацию с исходами лечения антипсихотиками [10,11].…”

Section: введение / Introductionunclassified

Analysis of associations between pharmacodynamic genetic factors and antipsychotics’ effectiveness and safety in adolescents with acute psychotic episodes taking antipsychotics during a 28-day follow-up

Ivashchenko

Федина

Буромская

et al. 2021

GCP

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Introduction. Antipsychotics are the main drugs for treatment of schizophrenia spectrum disorders. Pharmacodynamic genetic factors are being actively studied to improve the accuracy of antipsychotic selection based on pharmacogenetic testing. Purpose of this study: to establish associations of genetic polymorphisms of the DRD2, DRD3, DRD4, HTR2A, COMT, ZNF804A, and ANKS1B genes with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode during a 28-day follow-up. Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD-10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms DRD2 rs1800497 (C>T), DRD3 rs6280 (C>T), DRD3 rs324026 (C>T), DRD4 rs1800955 (C>T), HTR2A rs6313 (T>C), COMT rs4680 (Val158Met, G>A), ZNF804A rs1344706 (A>C), ANKS1B rs7968606 (C>T) by real-time PCR. Results. DRD2 rs1800497 T allele carriers had a stronger reduction in the PANSS subscore «Productive Symptomatics» on day 14 (Me=-7.0 [-9.0;-5.0] vs Me=-7.0 [-8.0;-2.0]; p=0.018) and day 28 of follow-up (Me=-11.0 [-9.0;-5.5] vs Me=-8.0 [-8.0;-2.0]; p=0.019). Also, greater improvement on the CGAS scale on day 14 of follow-up was seen in TC+CC HTR2A rs6313 carriers (Me=2.0 [1.0;3.0] vs. Me=2.0 [1.0;2.0]; p=0.029). DRD3 rs324026 homozygous carriers (TT) had a significantly lower SAS score (Me=0.5 [0.0; 1.0] vs. Me=1.0 [0.0; 5.0]; p=0.016) and UKU subscore «Neurological Disorders» on 28 days of antipsychotic therapy (Me=0.0 [0.0; 0.0] vs. Me=1.0 [0.0; 3.8]; p=0.005). DRD3 rs324026 TT carriers also had lower severity of akathisia according to the BARS scale. Carriers of the T DRD4 rs1800955 allele had a higher SAS scale score on day 28 of therapy compared with CC homozygotes (Me=1.0 [0.0;4.0] vs Me=0.0 [0.0;1.0]; p=0.036). Conclusion. The DRD2 rs1800497 was a predictor of better reduction of productive symptoms; HTR2A rs6313 demonstrated a similar association. The DRD2 rs1800497 polymorphic variant was a predictor of better reduction of productive symptomatology; HTR2A rs6313 demonstrated a similar association. DRD3 rs324026 and HTR2A rs6313 were associated with a lower frequency of neurological adverse reactions and akathisia. In contrast, carriers of the DRD4 rs1800955 were more prone to adverse reactions on pharmacotherapy.

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Association between dopamine receptor gene polymorphisms and effects of risperidone treatment: A systematic review and meta‐analysis

Cited by 19 publications

References 29 publications

Association study between <em>COMT</em>, <em>DRD2</em>, and <em>DRD3</em> gene variants and antipsychotic treatment response in Mexican patients with schizophrenia

Association study between <em>COMT</em>, <em>DRD2</em>, and <em>DRD3</em> gene variants and antipsychotic treatment response in Mexican patients with schizophrenia

Expression of Dopamine-Related Genes in Four Human Brain Regions

Analysis of associations between pharmacodynamic genetic factors and antipsychotics’ effectiveness and safety in adolescents with acute psychotic episodes taking antipsychotics during a 28-day follow-up

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