Association of 5-HTR2A T102C and A-1438G polymorphisms with clinical response to atypical antipsychotic treatment in schizophrenia: A meta-analysis

Yan, Pu; Gao, Bing; Wang, Shuqi; Wang, Shengdong; Li, Jing; Song, Meijuan

doi:10.1016/j.neulet.2021.136395

Cited by 6 publications

(11 citation statements)

References 24 publications

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“…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 ].…”

Section: Resultsmentioning

confidence: 99%

“…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 ).…”

Section: Resultsmentioning

confidence: 99%

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

Teng

Sandhu

Liemburg

et al. 2023

JPM

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The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010–2022, we identified 501 records. We included 29 meta-analyses constituting pooled data from 298 original studies over 69 PGx variants across 39 genes, 4 metabolizing phenotypes of CYP2D9, and 3 of CYP2C19. We observed weak unadjusted nominal significant (p < 0.05) additive effects of PGx variants of DRD1, DRD2, DRD3, HTR1A, HTR2A, HTR3A, and COMT (10 variants) on antipsychotic response; DRD2, HTR2C, BDNF, ADRA2A, ADRB3, GNB3, INSIG2, LEP, MC4R, and SNAP25 (14 variants) on weight gain; HTR2C (one variant) on metabolic syndrome; DRD2 (one variant) on prolactin levels; COMT and BDNF (two variants) on TD; HLA-DRB1 (one variant) on CLA; CYP2D6 (four phenotypes) and CYP2C19 (two phenotypes) on antipsychotics plasma levels. In the future, well-designed longitudinal naturalistic multi-center PGx studies are needed to validate the effectiveness of PGx variants in antipsychotic outcomes before establishing any reproducible PGx passport in clinical practice.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Teng

Sandhu

Liemburg

et al. 2023

JPM

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“…The most important polymorphisms are the 1438A/G promoter polymorphism, which is linked to lower promoter activity and receptor protein expression (Yan et al 2022), the 102T/C silent polymorphism within the coding region, which is in complete linkage disequilibrium with the previous one, and the His452Tyr (1354C/T) polymorphism, which is linked to an amino acid substitution within the receptor's cytoplasmic C-terminal. (Yan et al 2022) This alteration has no effect on expression or substrate binding to the receptor, but it does render it useless. The 452Tyr allele is more common in schizophrenia individuals who do not respond to clozapine therapy.…”

Section: -Ht2ramentioning

confidence: 99%

“…Among clozapine non-responders and schizophrenia patients with established TD, this allele is considerably overexpressed. Because this is a quiet polymorphism, an epigenetic process like methylation is thought to be responsible for 102C>T SNP functioning (Yan et al 2022).…”

Section: -Ht2ramentioning

confidence: 99%

Olanzapine Use in Schizophrenia and the Modulation of Its Response by Genetic Variations

2022

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Schizophrenia is a chronic disease with diverse psychopathology and multiple phases of illness. Consequently, numerous factors must be considered when assessing the benefits of a given treatment over short- and long-term periods. Olanzapine is an atypical antipsychotic reported to be effective without producing many of the disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. Despite the fact that olanzapine is still associated with a known risk of metabolic side effects, including weight gain, many clinicians continue to prescribe olanzapine for the treatment of schizophrenia with the expectation of additional therapeutic antipsychotic efficacy relative to other first-line atypical antipsychotics. This review focuses on the epidemiology, pathogenesis, and treatment of schizophrenia with special emphasis on the role of olanzapine in the treatment of schizophrenia. Genetic variants associated with the therapeutic efficacy and adverse effects of olanzapine are reviewed and those with the potential to act as a clinical predictor of therapeutic response and/or adverse effects are discussed. Recommendations are made for the use of some of these genetic variants in clinical medicine.

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“…e HTR2A gene that encodes the 5-HT2A receptor (5-hydroxytryptamine (serotonin) receptor 2A) is localized on the 13q14-q21 chromosome. is gene is involved in the serotonin system and is o en of interest to scientists who have been searching for genetic associations of various psychopathologies such as schizophrenia (González-Castro et al, 2013;Mistry et al, 2011;Yan et al, 2021), but the features of its relationship with emotional and cognitive processes in healthy people have not been su ciently studied.…”

Section: Introductionmentioning

confidence: 99%

Recognition of Emotional and Neutral Visual Scenes in Carriers of the MAOA, COMT, DRD4, and 5HT2A Gene Polymorphisms

Ермаков¹,

Vorobyeva²,

Denisova³

et al. 2022

Psych. Rus.

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Background. It is known that some genes regulate neurochemical metabolism, and their polymorphisms a" ect cognitive performance, including the ability to categorize emotionally signi# cant information. Objective. ! e aim of our study was to analyze the recognition of emotional and neutral visual scenes in carriers of di" erent polymorphic variants of the MAOA, COMT, DRD4, and 5HT2A genes. Design. ! e study sample consisted of 87 university students (Caucasians, women 63%, average age 20.4±2.6 years). ! e genotypes of the COMT, 5HT2A, and DRD4 genes were determined by polymerase chain reaction. Agarose gel electrophoresis was used to determine the number of tandem repeats of the MAOA gene. ! ree hundred sixty (360) photographic images of scenes of di" erent emotional valence (positive, negative, and neutral — 120 images for each category) were used as stimuli. ! ese images were classi# ed by expert assessments. ! e images were presented in a random sequence. ! e exposure time was 700 ms. ! e research participants were asked to determine the emotional valence of each scene. Results. We found that only the COMT gene genotype a" ected the recognition of emotional and neutral visual scenes. Carriers of the COMT Val/Val genotype, which causes dopamine to stay in the synaptic space for a shorter time, are better in recognizing and demonstrate higher sensitivity to the emotional content of scenes. Carriers of the Val/Met genotype demonstrated the worst ability to di" erentiate the emotional valence of visual scenes. Conclusion. ! is study has shown that the length of stay of monoamines in the synaptic space regulated by the COMT gene a" ects the recognition of emotional visual information.

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Association of 5-HTR2A T102C and A-1438G polymorphisms with clinical response to atypical antipsychotic treatment in schizophrenia: A meta-analysis

Cited by 6 publications

References 24 publications

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

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

Olanzapine Use in Schizophrenia and the Modulation of Its Response by Genetic Variations

Recognition of Emotional and Neutral Visual Scenes in Carriers of the MAOA, COMT, DRD4, and 5HT2A Gene Polymorphisms

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