Catecholamine-related gene expression in blood correlates with tic severity in tourette syndrome.
Tourette syndrome (TS) is a heritable disorder characterized by tics that are decreased in some patients by treatment with alpha adrenergic agonists and dopamine receptor blockers. Thus, this study examines the relationship between catecholamine gene expression in blood and tic severity. TS diagnosis was confirmed using Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and tic severity measured using the Yale Global Tic Severity Scale (YGTSS) for 26 un-medicated subjects with TS. Whole blood was collected and Ribonucleic acid (RNA) processed on Affymetrix Human Exon 1.0 ST arrays. An Analysis of Covariance (ANCOVA) identified 3627 genes correlated with tic severity (p<0.05). Searches of Medical Subject Headings, Gene Ontology, Allen Mouse Brain Atlas, and PubMed determined genes associated with catecholamines and located in the basal ganglia. Using GeneCards, PubMed, and manual curation, seven genes associated with TS were further examined: DRD2, HRH3, MAOB, BDNF, SNAP25, SLC6A4, and SLC22A3. These genes are highly associated with TS and have also been implicated in other movement disorders, Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive-Compulsive Disorder (OCD). Correlation of gene expression in peripheral blood with tic severity may allow inferences about catecholamine pathway dysfunction in TS subjects. Findings built on previous work suggest that at least some genes expressed peripherally are relevant for central nervous system (CNS) pathology in the brain of individuals with TS.
Department of Neurology and MIND Institute, University of California at Davis, 2805 50th Street, Sacramento, CA 95817, USA. joan.gunther@ucdmc.ucdavis.edu
Joan
J
Gunther
Yingfang
Y
Tian
Boryana
B
Stamova
Lisa
L
Lit
Blythe
B
Corbett
Brad
B
Ander
Xinhua
X
Zhan
Glen
G
Jickling
Netty
N
Bos-Veneman
Da
D
Liu
Pieter
P
Hoekstra
Frank
F
Sharp
D000293:Adolescent; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002648:Child; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012720:Severity of Illness Index; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics; D020323:Tics / Q000235:genetics*; D005879:Tourette Syndrome / Q000235:genetics*; D000099254:Organic Cation Transporter 3
D019208:Brain-Derived Neurotrophic Factor; D008995:Monoamine Oxidase; D027701:Organic Cation Transport Proteins; D017448:Receptors, Dopamine D2; D050486:Serotonin Plasma Membrane Transport Proteins; D050825:Synaptosomal-Associated Protein 25; D000099254:Organic Cation Transporter 3; C493230:SLC6A4 protein, human