ArticleBiological psychiatry2013
Multiple regulatory variants modulate expression of 5-hydroxytryptamine 2A receptors in human cortex.
Article in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Association of serotonin receptor gene polymorphisms with anorexia nervosa: a systematic review and meta-analysis.Eating and weight disorders : EWD · 2024Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants.Clinical pharmacology and therapeutics · 2023Guideline
- Potential diagnostic markers of olanzapine efficiency for acute psychosis: a focus on peripheral biogenic amines.BMC psychiatry · 2017Trial
- Observational
- Article
- Pharmacogenetic Factors Influence Escitalopram Pharmacokinetics and Adverse Events in Youth with a Family History of Bipolar Disorder: A Preliminary Study.Journal of child and adolescent psychopharmacology · 2024Article
- Examining Whether Genetic Variants Moderate the Skeletal Effects of Selective Serotonin Reuptake Inhibitors in Older Adolescents and Young Adults.Journal of child and adolescent psychopharmacology · 2023Observational
- The contribution of the 5-hydroxytryptamine receptor 2 A gene polymorphisms rs6311 and rs6313 to Schizophrenia in Iran.Molecular biology reports · 2023Article
- Genetic polymorphisms in the serotonin, dopamine and opioid pathways influence social attention in rhesus macaques (Macaca mulatta).PloS one · 2023Article
- Identification and discovery of imaging genetic patterns using fusion self-expressive network in major depressive disorder.Frontiers in neuroscience · 2023Article
- Genetic and epigenetic analysis of the serotonin 2A receptor in the context of cocaine abuse.Epigenetics · 2022Article
- Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (Biomedicines · 2022Article
- Proteomics analysis of the gut-brain axis in a gut microbiota-dysbiosis model of depression.Translational psychiatry · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Aberrant alternative splicing ofHeliyon · 2020Article
- Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels.Human brain mapping · 2020Article
- Analysis of the Deleterious Single-Nucleotide Polymorphisms Associated With Antidepressant Efficacy in Major Depressive Disorder.Frontiers in psychiatry · 2020Article
- Connection between polymorphisms inJournal of genetics · 2019Article
- Quantification of allelic differential expression using a simple Fluorescence primer PCR-RFLP-based method.Scientific reports · 2019Article
- The Interaction of TPH2 and 5-HT2A Polymorphisms on Major Depressive Disorder Susceptibility in a Chinese Han Population: A Case-Control Study.Frontiers in psychiatry · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe 5-hydroxytryptamine 2A receptor, encoded by HTR2A, is a major postsynaptic target for serotonin in the human brain and a therapeutic drug target. Despite hundreds of genetic associations investigating HTR2A polymorphisms in neuropsychiatric disorders and therapies, the role of genetic HTR2A variability in health and disease remains uncertain.
methodsTo discover and characterize regulatory HTR2A variants, we sequenced whole transcriptomes from 10 human brain regions with massively parallel RNA sequencing and measured allelic expression of multiple HTR2A messenger (m)RNA transcript variants. Following discovery of functional variants, we further characterized their impact on genetic expression in vitro.
resultsThree polymorphisms modulate the use of novel alternative exons and untranslated regions (UTRs), changing expression of RNA and protein. The frequent promoter variant rs6311, widely implicated in human neuropsychiatric disorders, decreases usage of an upstream transcription start site encoding a longer 5'UTR with greater translation efficiency. rs76665058, located in an extended 3'UTR and unique to individuals of African descent, modulates allelic HTR2A mRNA expression. The third single nucleotide polymorphism, unannotated and present in only a single subject, directs alternative splicing of exon 2. Targeted analysis of HTR2A in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study reveals associations between functional variants and depression severity or citalopram response.
conclusionsRegulatory polymorphisms modulate HTR2A mRNA expression in an isoform-specific manner, directing the usage of novel untranslated regions and alternative exons. These results provide a foundation for delineating the role of HTR2A and serotonin signaling in central nervous system disorders.
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