Download pdf
Research Progress on the Relationship Between the Regulation of SLC6A4 Gene and Anxiety Disorders
- 1 Shanghai University, Shanghai, China
* Author to whom correspondence should be addressed.
Abstract
Anxiety disorder is one of the most common mental disorders. Numerous studies have demonstrated the critical role played by genetic variables in the etiology of anxiety disorders. SLC6A4, which encodes serotonin transporter, is considered to be an important gene associated with anxiety susceptibility. The SLC6A4 gene's upstream promoter has a polymorphism region that has an impact on the transcriptional activity of the gene. Research has shown that this promoter polymorphism has a certain relationship with the occurrence of anxiety disorders and drug treatment. Anxiety disorders are also linked to SLC6A4 gene methylation and intron 2 (Stin2) polymorphism. Stin2 point and SLC6A4 gene methylation are all related to gene expression. This review summarizes the current research on the relationship between SLC6A4 gene promoter polymorphism, Stin2 polymorphism, and SLC6A4 gene methylation in the pathogenesis and drug treatment of anxiety disorder, to understand the current research progress of SLC6A4 gene expression in anxiety disorder.
Keywords
anxiety, SLC6A4, 5-HTTLPR, Stin2
[1]. J. Baxter, K. M. Scot, T. Vos & H. A, Whiteford. Global prevalence of anxiety disorders: a systematic review and meta-regression. Psychological Medicine 43, 897-910 (2013).
[2]. M. Shimada-Sugimoto, T. Otowa & J. M. Hettema. Genetics of anxiety disorders: Genetic epidemiological and molecular studies in humans. Psychiatry & Clinical Neurosciences 69, 388-401 (2015).
[3]. Arias, M. Aguilera, J. Moya. The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety‐related traits. Acta Psychiatr Scand 125, 194-202 (2012).
[4]. Heils, A. Teufel, S. Petri et al. Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry 66, 2621-2624 (1996)
[5]. Michaelovsky et al. A novel allele in the promoter region of the human serotonin transporter gene. Molecular Psychiatry (1999).
[6]. M. Nakamura, S. Ueno, A. Sano et al. The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 5, 32-38 (2000).
[7]. J. B. Kraft, S. L. Slager, P. J. Mcgrath & S. P. Hamilton. Sequence analysis of the serotonin transporter and associations with antidepressant response. Biological Psychiatry 58, 374-381 (2005).
[8]. Prasansuklab, Y. Poovorawan & T.Tencomnao. Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells. International Journal of Molecular Sciences 12, 6619-6634 (2011).
[9]. Hranilovic et al. Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression. Biological Psychiatry 55, 1090-1094 (2004).
[10]. M. Vijayendran et al. The relationship of the serotonin transporter (SLC6A4) extra long variant to gene expression in an African American sample. Am J Med Genet B Neuropsychiatr Genet 159B, 611-612 (2012)
[11]. J. B. Kraft, S. L. Slager, P. J. McGrath & S. P. Hamilton. Sequence analysis of the serotonin transporter and associations with antidepressant response. Biol Psychiatry 58, 374-381, doi:10.1016/j.biopsych.2005.04.048 (2005).
[12]. T. Ikegame et al. Identification and functional characterization of the extremely long allele of the serotonin transporter-linked polymorphic region. Transl Psychiatry 11, 119, doi:10.1038/s41398-021-01242-9 (2021)
[13]. Q. Zhao, L. I. Yu-Ling, Y. Liu & Y. Ding. Association between anxiety-depression and 5-HTTLPR gene polymorphism in school-aged twins. Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary PXediatrics 18, 61-66 (2016).
[14]. S. Riccardo, S.Catia, B.Cristian, M.Alessandra & G.Massimo. The influence of psychiatric screening in healthy populations selection: a new study and meta-analysis of functional 5-HTTLPR and rs25531 polymorphisms and anxiety-related personality traits. BMC Psychiatry 11 (2011)
[15]. B. R. Cornwell et al. The Unpredictive Brain Under Threat: A Neurocomputational Account of Anxious Hypervigilance. Biological Psychiatry, 447 (2017).
[16]. Chen et al. An integrative analysis of 5HTT-mediated mechanism of hyperactivity to non-threatening voices. Commun Biol 3, 113 (2020).
[17]. Bortoluzzi et al. Anxiety disorders and anxiety-related traits and serotonin transporter gene-linked polymorphic region (5-HTTLPR) in adolescents: case-control and trio studies. Psychiatr Genet 24, 176-180 (2014)
[18]. M. R. Munafo et al. 5-HTTLPR genotype and anxiety-related personality traits: a meta-analysis and new data. Am J Med Genet B Neuropsychiatr Genet 150B, 271-281, (2009)
[19]. N. Fogelman et al. Stressing over anxiety: A novel interaction of 5-HTTPLR genotype and anxiety-related phenotypes in older adults. Psychoneuroendocrinology 71, 36-42 (2016).
[20]. K. Mccormack et al. Serotonin transporter gene variation, infant abuse, and responsiveness to stress in rhesus macaque mothers and infants. Hormones & Behavior 55, 538-547 (2009).
[21]. Dalibor et al. Serotonin transporter gene (5-HTTLPR) polymorphism and efficacy of selective serotonin reuptake inhibitors--do we have sufficient evidence for clinical practice. Acta clinica Croatica (2013).
[22]. S. Won et al. Association between serotonin transporter-linked polymorphic region and escitalopram antidepressant treatment response in Korean patients with major depressive disorder. Neuropsychobiology 66, 221-229 (2012).
[23]. S. Ishiguro et al. Determinants of pharmacodynamic trajectory of the therapeutic response to paroxetine in Japanese patients with panic disorder. Eur J Clin Pharmacol 67, 1213-1221 (2011).
[24]. R. S. Sandeep Gyawalia et al. Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder. Biological Psychiatry R. S. Sandeep Gyawalia et al. Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder. Biological Psychiatry R. S. Sandeep Gyawalia et al. Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder. Biological Psychiatry 67, 331-338 (2010).
[25]. J. Lee et al. Serotonin transporter gene polymorphisms may be associated with poststroke neurological recovery after escitalopram use. J Neurol Neurosurg Psychiatry 89, 271-276 (2018).
[26]. MacKenzie & Quinn. A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo. Proceedings of the National Academy of Sciences of the United States of America (1999)
[27]. J. Bah et al. Serotonin transporter gene polymorphisms: effect on serotonin transporter availability in the brain of suicide attempters. Psychiatry Res 162, 221-229 (2008).
[28]. K. Ohara et al. A variable-number-tandem-repeat of the serotonin transporter gene and anxiety disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry 23, 55-65 (1999).
[29]. Sarosi et al. Association of the STin2 polymorphism of the serotonin transporter gene with a neurocognitive endophenotype in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 32, 1667-1672 (2008).
[30]. J. Popp, S.Leucht, S.Heres & W.Steimer. Serotonin transporter polymorphisms and side effects in antidepressant therapy--a pilot study. Pharmacogenomics 7, 159-166 (2006).
[31]. V. Ramesh, V. Venkatesan & B. Ramasamy. Role of serotonin transporter and receptor gene polymorphisms in treatment response to selective serotonin reuptake inhibitors in major depressive disorder. Hum Psychopharmacol 37, e2830, doi:10.1002/hup.2830 (2022)
[32]. D. K. Kim et al. Serotonin transporter gene polymorphism and antidepressant response. Neuroreport 11, 215-219 (2000).
[33]. M. Wilkie et al. Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy. Pharmacogenomics Journal.
[34]. J. S. Alasaari et al. Environmental Stress Affects DNA Methylation of a CpG Rich Promoter Region of Serotonin Transporter Gene in a Nurse Cohort. PLoS ONE 7, e45813- (2012).
[35]. M. S. Mendonca et al. Epigenetic variation at the SLC6A4 gene promoter in mother-child pairs with major depressive disorder. J Af ect Disord 245, 716-723, doi:10.1016/j.jad.2018.10.369 (2019)
[36]. D. Lam et al. Genotype-dependent associations between serotonin transporter gene (SLC6A4) DNA methylation and late-life depression. BMC Psychiatry 18, 282, doi:10.1186/s12888-018-1850-4 (2018).
Cite this article
Zheng,H. (2023). Research Progress on the Relationship Between the Regulation of SLC6A4 Gene and Anxiety Disorders. Theoretical and Natural Science,3,463-469.
Data availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
Disclaimer/Publisher's Note
The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of EWA Publishing and/or the editor(s). EWA Publishing and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
About volume
Volume title: Proceedings of the 2nd International Conference on Biological Engineering and Medical Science (ICBioMed 2022), Part I
© 2024 by the author(s). Licensee EWA Publishing, Oxford, UK. This article is an open access article distributed under the terms and
conditions of the Creative Commons Attribution (CC BY) license. Authors who
publish this series agree to the following terms:
1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons
Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this
series.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published
version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial
publication in this series.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and
during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See
Open access policy for details).