C825T polymorphism in the human G protein beta3 subunit gene is associated with long-term clozapine treatment-induced body weight change in the Chinese population

Wang, Daqing; Bai, Ya‐Mei; Chen, Jen-Yeu; Lin, Chao-Cheng; Lai, I-Ching; Liou, Ying‐Jay

doi:10.1097/01.fpc.0000175600.26893.fa

Cited by 93 publications

(88 citation statements)

References 35 publications

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“…There is no strong genetic evidence connecting histamine variants with treatment-related weight gain nor with other serotonin (5-HT2A, 5-HT6) or dopamine receptors (D2), G-protein-related proteins (GNB3) and metabolic enzymes (CYP2D6). 262,[264][265][266][267]276 Variants of the phenylalanine hydroxylase gene (PAH) were investigated for their possible relation with the increased level of phenylalanine observed in TD patients, but no significant associations were observed. 259 However, trends towards association with b 3 -and a 1A -adrenergic receptor variants, and with TNF-a polymorphisms in a study with a limited and heterogeneous sample indicate that further factors may contribute.…”

Section: Prediction Of Side Effectsmentioning

confidence: 99%

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

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The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid matabolizers (UMs) will need increased drug dosage to obtain therapeutic response. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. In particular, there is important evidence suggesting association between dopamine 2 receptor (D2) polymorphisms (Taq I and À141-C Ins/Del) and a dopamine 3 receptor (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive dyskinesia. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C polymorphism (À759ÀT/C) in antipsychotic-induced weight gain. Application of this knowledge to clinical practice is slowly gathering pace, with pretreatment determination of individual's drug metabolic rates, via CYP genotyping, leading the field. Genetic determination of patients' metabolic status is expected to bring clinical benefits by helping to adjust therapeutic doses and reduce adverse reactions. Genetic tests for the pretreatment prediction of antipsychotic response, although still in its infancy, have obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered as successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are far from being realized. Further development of genetic tests is required before the concept of tailored treatment can be applied to psychopharmatherapy. This review aims to summarize the key findings from the last decade of research in the field. Current knowledge on genetic prediction of drug metabolic status, general response and drug-induced side effects will be reviewed and future pharmacogenomic and epigenetic research will be discussed.

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Section: Prediction Of Side Effectsmentioning

confidence: 99%

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

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“…8 Candidate gene studies on antipsychotic-induced weight gain produced significant findings in the 5-HTR2C, GNB3 and ADR2A receptor genes. [9][10][11][12][13][14] CYP1A2 and, less significantly, CYP2D6 are involved in the metabolism of olanzapine. 15,16 The CYP1A2*1F (À163A) polymorphism (rs762551) has been associated with higher enzyme inducibility and higher clearance of CYP1A2 substrates such as melatonin 17 or caffeine in Caucasian smokers.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome

et al. 2009

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“…-825C/T T allele was associated with higher AIWG in several studies, and with a nonsignificant trend in a meta-analysis Ujike et al, 129 Wang et al, 138 Souza et al 184 …”

Section: Gnb3mentioning

confidence: 99%

“…136,137 Similarly, the T allele carriers of the -825C/T polymorphism in the gene encoding β3-subunit of G-protein receptors, that is, GNB3, are at higher risk for AIWG. 129,138 Other reported associations, such as polymorphisms in insulin-induced gene 2 (INSIG2), 139 have failed to be replicated in other samples. 125,140 Recent studies indicate an influence of DRD2 polymorphisms, 141,142 cholecystokinin B receptors, 143 and adiponectin.…”

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confidence: 99%

Pharmacogenetics of Antipsychotics

2014

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Objective: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors. Methods:We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses.Results: Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs. Conclusion:First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings. W W W La pharmacogénétique des antipsychotiquesObjectif : Au cours des dernières décennies, des efforts croissants ont été déployés dans des études visant à percer l'influence des facteurs génétiques sur le dosage des antipsychotiques (AP), la réponse au traitement, et la survenue d'effets indésirables. Ces études voulaient améliorer les soins cliniques en prédisant le résultat du traitement par AP, et en donnant lieu ainsi à des stratégies de traitement individualisées. Nous présentons les résultats les plus importants obtenus par des études tant de gènes candidats que d'association pangénomique, notamment les facteurs pharmacocinétiques et pharmacodynamiques. Méthodes :Nous avons passé en revue les études sur la pharmacogénétique de la réponse aux AP et des effets indésirables publiées dans PubMed jusqu'au début de 2012. Vu le nombre élevé d'études publiées, notre revue a mis l'accent sur les résultats qui ont été reproduits dans des études indépendantes ou qui sont soutenus par des méta-analyses.

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C825T polymorphism in the human G protein beta3 subunit gene is associated with long-term clozapine treatment-induced body weight change in the Chinese population

Abstract: the abundant 3435C > T SNP appears to be a main factor in allelic variation of ABCB1 mRNA expression in the liver, by changing mRNA stability.

Cited by 93 publications

References 35 publications

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome

Pharmacogenetics of Antipsychotics

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