Methylation of the serotonin reuptake transporter gene and non-motor symptoms in dystonia patients.

Humans DNA Methylation Serotonin Dystonia / genetics Dystonic Disorders / complications Serotonin Plasma Membrane Transport Proteins / genetics
Dystonia Epigenetics Methylation Non-motor symptoms Psychiatry SLC6A4 Serotonin reuptake transporter

Journal

Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977

Informations de publication

Date de publication:
11 Dec 2022
Historique:
received: 19 05 2022
accepted: 21 11 2022
entrez: 12 12 2022
pubmed: 13 12 2022
medline: 15 12 2022
Statut: epublish

Résumé

Dystonia is a rare movement disorder, in which patients suffer from involuntary twisting movements or abnormal posturing. Next to these motor symptoms, patients have a high prevalence of psychiatric comorbidity, suggesting a role for serotonin in its pathophysiology. This study investigates the percentage of DNA methylation of the gene encoding for the serotonin reuptake transporter (SLC6A4) in dystonia patients and the associations between methylation levels and presence and severity of psychiatric symptoms. Patients with cervical dystonia (n = 49), myoclonus dystonia (n = 41) and dopa-responsive dystonia (DRD) (n = 27) and a group of healthy controls (n = 56) were included. Psychiatric comorbidity was evaluated with validated questionnaires. Methylation levels of 20 CpG sites situated 69 to 213 base pairs upstream of the start codon of SLC6A4 were investigated. Methylation in dystonia patients was compared to healthy controls, correcting for age, and correlated with psychiatric comorbidity. Bootstrapped quantile regression analysis showed that being a dystonia patient compared to a healthy control significantly explains the methylation level at two CpG sites (CpG 24: pseudo-R This study showed an association between percentage of methylation at several specific sites of the promoter region of SLCA64 and (dopa-responsive) dystonia patients compared to healthy controls. Furthermore, methylation levels were associated with severity of anxiety and presence of a depressive disorder in the dystonia group. This study suggests alterations in the serotonergic metabolism in dystonia patients, and its relation with the non-motor symptoms.

Sections du résumé

BACKGROUND BACKGROUND
Dystonia is a rare movement disorder, in which patients suffer from involuntary twisting movements or abnormal posturing. Next to these motor symptoms, patients have a high prevalence of psychiatric comorbidity, suggesting a role for serotonin in its pathophysiology. This study investigates the percentage of DNA methylation of the gene encoding for the serotonin reuptake transporter (SLC6A4) in dystonia patients and the associations between methylation levels and presence and severity of psychiatric symptoms.
METHODS METHODS
Patients with cervical dystonia (n = 49), myoclonus dystonia (n = 41) and dopa-responsive dystonia (DRD) (n = 27) and a group of healthy controls (n = 56) were included. Psychiatric comorbidity was evaluated with validated questionnaires. Methylation levels of 20 CpG sites situated 69 to 213 base pairs upstream of the start codon of SLC6A4 were investigated. Methylation in dystonia patients was compared to healthy controls, correcting for age, and correlated with psychiatric comorbidity.
RESULTS RESULTS
Bootstrapped quantile regression analysis showed that being a dystonia patient compared to a healthy control significantly explains the methylation level at two CpG sites (CpG 24: pseudo-R
CONCLUSIONS CONCLUSIONS
This study showed an association between percentage of methylation at several specific sites of the promoter region of SLCA64 and (dopa-responsive) dystonia patients compared to healthy controls. Furthermore, methylation levels were associated with severity of anxiety and presence of a depressive disorder in the dystonia group. This study suggests alterations in the serotonergic metabolism in dystonia patients, and its relation with the non-motor symptoms.

Identifiants

DOI: 10.1186/s13148-022-01384-7 PMID: 36503539 PMC: PMC9743677
pubmed: 36503539
doi: 10.1186/s13148-022-01384-7
pii: 10.1186/s13148-022-01384-7
pmc: PMC9743677
doi:

Substances chimiques

Serotonin 333DO1RDJY
SLC6A4 protein, human 0
Serotonin Plasma Membrane Transport Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

170

Subventions

Organisme : Stichting De Cock-Hadders
ID : 2022-81
Organisme : Stichting De Cock-Hadders
ID : 2022-81
Organisme : Stichting De Cock-Hadders
ID : 2022-81

Informations de copyright

© 2022. The Author(s).

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Auteurs

Elze R Timmers (ER)

Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands. e.r.timmers@umcg.nl.
Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, The Netherlands. e.r.timmers@umcg.nl.

Torsten Plösch (T)

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Marenka Smit (M)

Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, The Netherlands.

Ingrid H Hof (IH)

Laboratory of Metabolic Diseases, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.

Rikst Nynke Verkaik-Schakel (RN)

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Marina A J Tijssen (MAJ)

Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, The Netherlands.

Tom J de Koning (TJ)

Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, The Netherlands.
Pediatrics, Department of Clinical Sciences, Lund University, Box 117, 221 00, Lund, Sweden.

Klary E Niezen-Koning (KE)

Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, The Netherlands.
Laboratory of Metabolic Diseases, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.

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questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Methylation of the serotonin reuptake...
questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Sérotonine › Methylation of the serotonin reuptake...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Dyskinésies › Dystonie › Methylation of the serotonin reuptake...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Troubles de la motricité › Troubles dystoniques › Methylation of the serotonin reuptake...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Transporteurs de la sérotonine › Methylation of the serotonin reuptake...