ReviewMolecular neurobiology2017
Looking Beyond the 5-HTTLPR Polymorphism: Genetic and Epigenetic Layers of Regulation Affecting the Serotonin Transporter Gene Expression.
Review in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 3 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Lack of association of the 5-HTTLPR polymorphism and brain serotonin transporter or receptor in healthy individuals: bayesian and frequentist meta-analyses.Brain imaging and behavior · 2026Pooled it
- Inhibition of the serotonin transporter and risk of heart valve disease: A systematic review and meta-analysis.European journal of pharmacology · 2026Pooled 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
- Trial
- Eight weeks of high-intensity interval training increases peripheral serotonin transporter expression independently of promoter methylation changes.European journal of applied physiology · 2026Article
- Integrated Metabolomic and Transcriptomic Analyses Reveal Alterations in the Serotonergic Synapse Pathway and a Robust Diagnostic Model in Ulcerative Colitis.Metabolites · 2026Article
- A Study of Candidate Genes Associated with Suicide Attempts in the Kazakh Population in Astana, Kazakhstan.International journal of molecular sciences · 2026Article
- Prematurity and Epigenetic Regulation ofBiomedicines · 2025Article
- Fibromyalgia: are you a genetic/environmental disease?Pain reports · 2025Review
- Hyperarousal, Dissociation, Emotion Dysregulation and Re-Experiencing-Towards Understanding Molecular Aspects of PTSD Symptoms.International journal of molecular sciences · 2025Review
- Reduced expression of the serotonin transporter impacts mitochondria in a sexually dimorphic manner.Biochemistry and biophysics reports · 2025Article
- Bidirectional crosstalk between microglia and serotonin signaling in neuroinflammation and CNS disorders.Frontiers in immunology · 2025Review
- Assessment of MIR3142HG genetic polymorphisms and the susceptibility of lumbar disc herniation in the Chinese population.Scientific reports · 2024Article
- Serotonin Transporter (SLC6A4) and FK506-Binding Protein 5 (FKBP5) Genotype and Methylation Relationships with Response to Meditation in Veterans with PTSD.Molecular neurobiology · 2024Article
- DNA Sequence Variations Affecting Serotonin Transporter Transcriptional Regulation and Activity: Do They Impact Alcohol Addiction?International journal of molecular sciences · 2024Article
- On the impulsivity path: Examining the unique and conjoint relations between emotion- and non-emotion-related impulsivity, internalizing symptoms, alcohol use, and physical health parameters.Journal of clinical psychology · 2024Article
- Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence.Clinical epigenetics · 2024Article
- Genes of cancer-related fatigue: a scoping review.Frontiers in oncology · 2024Article
- Predicting anxiety-related personality traits by means of serotonergic VNTR variants STin2 and 5-HTTLPR.Journal of mood and anxiety disorders · 2023Article
- DNA Methylation in Depression and Depressive-Like Phenotype: Biomarker or Target of Pharmacological Intervention?Current neuropharmacology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serotonin (5-HT) is a neurotransmitter that regulates fundamental aspects of brain development, physiology and behaviour. The serotonin transporter (5-HTT) is deputized to the reuptake of 5-HT from the intersynaptic space in the presynaptic neurons. 5-HTT governs duration and magnitude of 5-HT biological actions, acting as a master regulator of the fine-tuning of 5-HT signalling. Genetic variation at SLC6A4 gene locus, encoding 5-HTT, contributes to alteration in 5-HT reuptake. The 5-HTTLPR/rs25531/rs25532 polymorphisms located in the promoter region of SLC6A4 gene have been associated with stress-related psychopathology and functional brain phenotypes. Besides, further DNA variations in functional regulative elements located at 5' and 3' termini of the SLC6A4 gene influence transcriptional and post-transcriptional steps. Recently, epigenetic processes including SLC6A4 promoter methylation and transcript silencing by microRNA were shown to be involved in the aetiology of affective disorders. Furthermore, gene-environment interactions such as early life stress often encompass epigenetic changes, which can stably mark the genome in response to environmental stimuli potentially altering gene expression across lifespan. Therefore, it seems well established that functional variations in the SLC6A4 gene expression can no longer be ascribed to the modulating 5-HTTLPR promoter polymorphism but need to be integrated with the contribution arising from other interactive elements and epigenetic mechanisms. In this review, we discuss genetic and epigenetic layers of regulation affecting SLC6A4 gene expression. An overview of human and cellular studies investigating the impact of these regulatory processes on SLC6A4 gene expression is provided.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.