DRD3 Ser9Gly polymorphism and treatment response to antipsychotics in schizophrenia: A meta-analysis

The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis

“…They meta-analyzed the PGx variants in association with an antipsychotic response (11 meta-analysis studies; 20 variants across 10 genes), antipsychotic-induced weight/BMI gain (eight meta-analysis studies; 38 variants across 20 genes and four phenotypes of CYP2D6 ), metabolic syndrome (one meta-analysis study; three variants in HTR2C ), antipsychotic-related prolactin levels (two meta-analysis studies; two variants in DRD2 and four phenotypes of CYP2D6 ), antipsychotic-induced tardive dyskinesia (four meta-analysis studies; five variants across four genes), clozapine-induced agranulocytosis (one meta-analysis study; 13 PGx variants across nine genes), and plasma levels of antipsychotic drugs (three meta-analysis studies; two PGx variants in CYP1A2 , four phenotypes of CYP2D6 and three phenotypes of CYP2C19 ) ( Supplementary Tables S1 and S2 ). For treatment response, three meta-analysis studies reported in a mixed population, Caucasians and Asians separately [ 40 , 41 , 42 ]; one meta-analysis study reported in a mixed population and Caucasians [ 31 ]; six meta-analysis studies reported in mixed populations only [ 34 , 43 , 44 , 45 , 46 , 47 ]; one meta-analysis study reported in Asians [ 48 ]. For antipsychotic-induced weight/BMI gain, two meta-analysis studies reported in a mixed population, Caucasians and Asians separately [ 49 , 50 ]; two meta-analysis studies reported in a mixed population and Asians separately [ 51 , 52 ]; three meta-analysis studies reported in mixed population only [ 35 , 53 , 54 ]; one meta-analysis study did not state the ethnicity of the population [ 32 ].…”

“…Overall, 11 out of 29 included meta-analysis studies investigated the antipsychotic response. The studied antipsychotics included clozapine (five meta-analysis studies [ 31 , 34 , 40 , 41 , 47 ]), risperidone (two meta-analysis studies [ 41 , 48 ]), olanzapine (one meta-analysis study [ 41 ]), atypical antipsychotics combined together (two meta-analysis studies [ 40 , 41 ]), and all antipsychotics combined together (seven meta-analysis studies [ 40 , 42 , 43 , 44 , 45 , 46 , 47 ]). These studies examined the associations between 10 genes and response to either a specific antipsychotic or multiple antipsychotics combined ( Figure 3 , Supplementary Table S3 ).…”

“…Yet, no additive models were analyzed or raw data provided. While Hwang et al did not find any association between DRD3 rs6280 and clozapine response in mixed populations of Caucasians and African Americans [ 66 ], Liu et al reported that the rs6280*C allele was significantly associated with better treatment response to antipsychotics in Caucasians with a pooled odds ratio of 1.39 (95% CI: 1.12, 1.72; seven original studies), but not in Asians or African Americans [ 42 ].…”

“…For CYP2D6 and CYP2C19 , the number inside represents the number of phenotypes of this enzyme analyzed. References: Study 1, Hwang, 2010 [ 34 ]; 2, Zhang, 2010 [ 46 ]; 3 de Matos, 2015 [ 47 ]; 4, Huang, 2016 [ 43 ]; 5, Gressier, 2016 [ 31 ]; 6, Cargnin, 2016 [ 40 ]; 7, Takekita, 2016 [ 44 ]; 8, Ma, 2019 [ 48 ]; 9, Yoshikawa, 2020 [ 45 ]; 10, Yan, 2022 [ 41 ]; 11, Liu, 2022 [ 42 ]; 12, Sicard, 2010 [ 35 ]; 13, Shen, 2014 [ 51 ]; 14, Ma, 2014 [ 49 ]; 15, Zhang, 2016 [ 32 ]; 16, Suetani, 2017 [ 53 ]; 17, Yoshida, 2020 [ 52 ]; 18, Chen, 2020 [ 50 ]; 19, Wannasuphoprasit, 2021 [ 54 ]; 20, Miura, 2016 [ 55 ]; 21, Calafato, 2020 [ 56 ]; 22, Zai, 2010a [ 59 ]; 23, Zai, 2010b [ 60 ]; 24, Miura, 2014 [ 57 ]; 25, Lv, 2016 [ 58 ]; 26, Islam, 2022 [ 61 ]; 27, Takuathung, 2019 [ 64 ]; 28, Zhang, 2019 [ 63 ]; 29, Milosavljevic, 2021 [ 62 ]. Abbreviation: Chr, chromosome; AP, antipsychotics; AIWG, antipsychotic-induced weight gain; MetS, metabolic syndrome; PRL, prolactin; TD, tardive dyskinesia; CIA, clozapine-induced agranulocytosis.…”

Dopamine D1–D5 Receptors in Brain Nuclei: Implications for Health and Disease

“…A functional SNP in the D3 receptor, the DRD3 gene (Ser9Gly), has been shown to influence the affinity of the D3 receptor for dopamine and the efficacy of antipsychotic treatment [76]. This variant has also been associated with Parkinson's disease, especially in patients with cognitive impairment or psychosis [67].…”