GABA- and acetylcholine-related gene expression in blood correlate with tic severity and microarray evidence for alternative splicing in Tourette syndrome: a pilot study.
Tourette syndrome (TS) is a complex childhood neurodevelopmental disorder characterized by motor and vocal tics. Recently, altered numbers of GABAergic-parvalbumin (PV) and cholinergic interneurons were observed in the basal ganglia of individuals with TS. Thus, we postulated that gamma-amino butyric acid (GABA)- and acetylcholine (ACh)-related genes might be associated with the pathophysiology of TS. Total RNA isolated from whole blood of 26 un-medicated TS subjects and 23 healthy controls (HC) was processed on Affymetrix Human Exon 1.0 ST arrays. Data were analyzed to identify genes whose expression correlated with tic severity in TS, and to identify genes differentially spliced in TS compared to HC subjects. Many genes (3627) correlated with tic severity in TS (p < 0.05) among which GABA- (p = 2.1 × 10⁻³) and ACh- (p = 4.25 × 10⁻⁸) related genes were significantly over-represented. Moreover, several GABA and ACh-related genes were predicted to be alternatively spliced in TS compared to HC including GABA receptors GABRA4 and GABRG1, the nicotinic ACh receptor CHRNA4 and cholinergic differentiation factor (CDF). This pilot study suggests that at least some of these GABA- and ACh-related genes observed in blood that correlate with tics or are alternatively spliced are involved in the pathophysiology of TS and tics.
University of California at Davis, M.I.N.D., Institute and Department of Neurology, USA.
Yingfang
Y
Tian
Joan R
JR
Gunther
Isaac H
IH
Liao
Dazhi
D
Liu
Bradley P
BP
Ander
Boryana S
BS
Stamova
Lisa
L
Lit
Glen C
GC
Jickling
Huichun
H
Xu
Xinhua
X
Zhan
Frank R
FR
Sharp
D000293:Adolescent; D017398:Alternative Splicing / Q000235:genetics*; D000704:Analysis of Variance; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000235:genetics; D008297:Male; D010865:Pilot Projects; D012313:RNA / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics; D012720:Severity of Illness Index; D005879:Tourette Syndrome / Q000235:genetics* / Q000503:physiopathology
D053605:Leukemia Inhibitory Factor; D012313:RNA; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; C546260:GABRA4 protein, human; C528795:GABRG1 protein, human