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

Genes

Christina Dahl¹  Per Guldberg¹  Zeynep Tümer²  Mathis Hildonen²  VictoriaA. Bjerregaard²  AmandaM. Levy²  Lisbeth Birk Møller²  NanetteM. Debes³ 

[1] Danish Cancer Society Research Center, 2100 Copenhagen, Denmark;Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark;Tourette Clinics, Department of Paediatrics, Copenhagen University Hospital, 2730 Herlev, Denmark;

关键词: SERT;    SLC6A4;    5-HTT;    Gilles de la Tourette syndrome;    GTS;    OCD;   

DOI  :  10.3390/genes12010086

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown