Elevated Expression of SLC6A4 Encoding the Serotonin Transporter (SERT) in Gilles de la Tourette Syndrome

Mathis Hildonen; Amanda M Levy; Christina Dahl; Victoria A Bjerregaard; Lisbeth Birk Møller; Per Guldberg; Nanette M Debes; Zeynep Tümer

doi:10.3390/genes12010086

Elevated Expression of SLC6A4 Encoding the Serotonin Transporter (SERT) in Gilles de la Tourette Syndrome

Genes (Basel). 2021 Jan 12;12(1):86. doi: 10.3390/genes12010086.

Authors

Mathis Hildonen¹, Amanda M Levy¹, Christina Dahl², Victoria A Bjerregaard¹, Lisbeth Birk Møller^{1

3}, Per Guldberg^{2

4}, Nanette M Debes⁵, Zeynep Tümer^{1

6}

Affiliations

¹ Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark.
² Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.
³ Institute for Nature, Systems and Models, Roskilde University Center, 4000 Roskilde, Denmark.
⁴ Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.
⁵ Tourette Clinics, Department of Paediatrics, Copenhagen University Hospital, 2730 Herlev, Denmark.
⁶ Deparment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2020 Copenhagen, Denmark.

Abstract

Gilles de la Tourette syndrome (GTS) is a complex neurodevelopmental disorder characterized by motor and vocal tics. Most of the GTS individuals have comorbid diagnoses, of which obsessive-compulsive disorder (OCD) and attention deficit-hyperactivity disorder (ADHD) are the most common. Several neurotransmitter systems have been implicated in disease pathogenesis, and amongst these, the dopaminergic and the serotonergic pathways are the most widely studied. In this study, we aimed to investigate whether the serotonin transporter (SERT) gene (SLC6A4) was differentially expressed among GTS individuals compared to healthy controls, and whether DNA variants (the SERT-linked polymorphic region 5-HTTLPR, together with the associated rs25531 and rs25532 variants, and the rare Ile425Val variant) or promoter methylation of SLC6A4 were associated with gene expression levels or with the presence of OCD as comorbidity. We observed that SLC6A4 expression is upregulated in GTS individuals compared to controls. Although no specific genotype, allele or haplotype was overrepresented in GTS individuals compared to controls, we observed that the L_AC/L_AC genotype of the 5-HTTLPR/rs25531/rs25532 three-locus haplotype was associated with higher SLC6A4 mRNA expression levels in GTS individuals, but not in the control group.

Keywords: 5-HTT; GTS; Gilles de la Tourette syndrome; OCD; SERT; SLC6A4; expression; methylation; obsessive compulsive disorder; serotonin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution
Attention Deficit Disorder with Hyperactivity / genetics
Attention Deficit Disorder with Hyperactivity / metabolism
Gene Expression Regulation*
Humans
Male
Mutation, Missense*
Obsessive-Compulsive Disorder / genetics
Obsessive-Compulsive Disorder / metabolism
Polymorphism, Genetic*
Serotonin Plasma Membrane Transport Proteins* / biosynthesis
Serotonin Plasma Membrane Transport Proteins* / genetics
Tourette Syndrome* / genetics
Tourette Syndrome* / metabolism

Substances

SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins