Association of
 HTR2C
 , But Not
 LEP
 or
 INSIG2
 , Genes with Antipsychotic-Induced Weight Gain in a German Sample

Opgen‐Rhein, Carolin; Brandl, Eva J.; Müller, Daniel J.; Neuhaus, Andres H.; Tiwari, Arun K.; Sander, Thomas; Dettling, Michael

doi:10.2217/pgs.10.50

Cited by 72 publications

(62 citation statements)

References 53 publications

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“…Most consistent findings exist for an association between polymorphisms of the HTR2C gene and AIWG. The functional polymorphism -759C/T 122 has repeatedly been shown to influence AIWG, with the C allele being overrepresented in patients with higher AIWG (for example, see Reynolds et al, 123 Miller et al, 124 and Opgen-Rhein et al, 125 including 2 metaanalyses, see De Luca et al 126 and Sicard et al 127 ). Although negative findings have been reported, 128,129 with one study indicating the opposite allele as a risk variant, 130 to date, the role of this polymorphism is supported by the most robust studies.…”

Section: Antipsychotic-induced Weight Gainmentioning

confidence: 99%

“…Although negative findings have been reported, 128,129 with one study indicating the opposite allele as a risk variant, 130 to date, the role of this polymorphism is supported by the most robust studies. Other HTR2C polymorphisms have been shown to be associated with AIWG as well, including the -995G/A, -1165A/G, 125 and Cys23Ser polymorphisms as part of a high risk haplotype. 127 Leptin plays a major role in energy homoeostasis.…”

Section: Antipsychotic-induced Weight Gainmentioning

confidence: 99%

“…The -2548A/G polymorphism in the encoding gene leptin (LEP) has been shown to impact on AIWG, with the G allele being the risk allele in some but not in all studies. 131,132 Nonetheless, negative findings (for example, see OpgenRhein et al 125 ; for review, see Lett et al 14 …”

Section: Antipsychotic-induced Weight Gainmentioning

confidence: 99%

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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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Section: Antipsychotic-induced Weight Gainmentioning

confidence: 99%

Section: Antipsychotic-induced Weight Gainmentioning

confidence: 99%

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Pharmacogenetics of Antipsychotics

2014

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“…16 Several studies linking HTR2C (Cys23Ser and -759C.T) polymorphisms to weight gain have been conducted, with significant [57][58][59][60] and nonsignificant [136][137][138][139][140] results. A recent meta-analysis of 522 schizophrenia individuals suggested that the -759C allele is associated with weight gain.…”

Section: Studies Assessing the Adverse Effects Of Clozapinementioning

confidence: 99%

“…144 Other genes with significant associations include ADRA2A, 51,52 BDNF, 53 DRD2, 54,55 adiponectin, C1Q and collagen domain containing (ADIPOQ), 50 melanocortin 4 receptor (MC4R), 63 protein kinase beta 2 non-catalytic subunit (PRKAB2), 65 protein kinase gamma 2 non-catalytic subunit (PRKAG2), 50 and roundabout axon guidance receptor homolog 1 (ROBO1). 66 Controversial results were observed for HTR2A 57,136 (positive and negative results, respectively), insulin induced gene 2 (INSIG2) 60,61,145 (positive results only in the second study), leptin (LEP) 60,62 (negative and positive results, respectively), protein kinase alpha 2 catalytic subunit (PRKAA2) 50,65 (negative and positive results, respectively), and TNF 67,137,146 (positive results only in the second study). No correlation was observed for adrenoreceptor beta 3 (ADRB3), 144 cholecystokinin (CCK), 147 cannabinoid receptor 1 (CNR1), 148 fatty acid binding protein 3 (FABP3), 50 fat mass and obesity associated (FTO), 50 peroxisome proliferator-activated receptor gamma (PPARG), 149 protein kinase alpha 1 catalytic subunit (PRKAA1), 50 protein kinase gamma 1 non-catalytic subunit (PRKAG1), 50 protein kinase gamma 3 non-catalytic subunit (PRKAG3), 50 72,73 were associated with risk of metabolic syndrome induced by clozapine or risperidone/olanzapine.…”

Section: Studies Assessing the Adverse Effects Of Clozapinementioning

confidence: 99%

Pharmacogenetics in schizophrenia: a review of clozapine studies

Kohlrausch

2013

Rev. Bras. Psiquiatr.

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Objectives: Clozapine is quite effective to treat schizophrenia, but its use is complicated by several factors. Although many patients respond to antipsychotic therapy, about 50% of them exhibit inadequate response, and ineffective medication trials may entail weeks of unremitted illness, potential adverse drug reactions, and treatment nonadherence. This review of the literature sought to describe the main pharmacogenetic studies of clozapine and the genes that potentially influence response to treatment with this medication in schizophrenics. Methods: We searched the PubMed database for studies published in English in the last 20 years using keywords related to the topic. Results and Conclusions: Our search yielded 145 studies that met the search and selection criteria. Of these, 21 review articles were excluded. The 124 studies included for analysis showed controversial results. Therefore, efforts to identify key gene mechanisms that will be useful in predicting clozapine response and side effects have not been fully successful. Further studies with new analysis approaches and larger sample sizes are still required.

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Bioinformatic analyses to select phenotype affecting polymorphisms in HTR2C gene

Piva

Giulietti

Baldelli

et al. 2011

Human Psychopharmacology

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Objective Single nucleotide polymorphisms (SNPs) in serotonin related genes influence mental disorders, responses to pharmacological and psychotherapeutic treatments. In planning association studies, researchers that want to investigate new SNPs have to select some among a large number of candidates. Our aim is to guide researchers in the selection of the most likely phenotype affecting polymorphisms. Here, we studied serotonin receptor 2C (HTR2C) SNPs because, till now, only relatively few of about 2000 are investigated.Methods We used the most updated and assessed bioinformatic tools to predict which variations can give rise to biological effects among 2450 HTR2C SNPs. Results We suggest 48 SNPs that are worth considering in future association studies in the field of psychiatry, psychology and pharmacogenomics. Moreover, our analyses point out the biological level probably affected, such as transcription, splicing, miRNA regulation and protein structure, thus allowing to suggest future molecular investigations. Conclusions Although few association studies are available in literature, their results are in agreement with our predictions, showing that our selection methods can help to guide future association studies.

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Association of HTR2C , But Not LEP or INSIG2 , Genes with Antipsychotic-Induced Weight Gain in a German Sample

Cited by 72 publications

References 53 publications

Pharmacogenetics of Antipsychotics

Pharmacogenetics of Antipsychotics

Pharmacogenetics in schizophrenia: a review of clozapine studies

Bioinformatic analyses to select phenotype affecting polymorphisms in HTR2C gene

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