Abstract
BackgroundGenetic factors are important in the pathogenesis of Tourette syndrome (TS). Notably, Dopamine receptor D2 (DRD2) gene has been suggested as a possible candidate gene for this disorder. Several studies have demonstrated that DRD2/ANKK1 TaqIA polymorphism is associated with an increased risk of developing TS. However, past results remain conflicting. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS.MethodsLiterature was searched in multiple databases including PUBMED, COCHRANE and WEB OF SCIENCE up to July 2014. The number of the genotypes for DRD2/ANKK1 TaqIA in the TS and control subjects was extracted and statistical analysis was performed using Review Manager 5.0.16 and Stata 12.0 software. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were utilized to calculate the risk of TS with DRD2/ANKK1 TaqIA. Stratified analysis based on ethnicity was also conducted.Results523 patients with TS, 564 controls and 87 probands plus 152 relatives from five published studies were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the DRD2/ANKK1 TaqIA A1 allele were 1.69 (95%CIs = 1.42-2.00) in the fixed-effect model and 1.66 (95%CIs = 1.33-2.08) in the random-effects model. Stratification by ethnicity indicated the TaqIA A1 allele was significantly associated with TS in Caucasians (fixed-effect model: OR=1.75, 95%CI = 1.43-2.16; random-effect model: OR=1.69, 95%CI = 1.25-2.28) and in Asians (OR=1.54, 95%CI = 1.12-2.10). Meta-analysis of the A1A1 vs. A2A2 (homozygous model), A1A2 vs. A2A2 (heterozygous model) and A1A1+A1A2 vs. A2A2 (dominant model) of this polymorphism revealed a significant association with TS in overall populations and Caucasians.ConclusionsThis meta-analysis suggested that the DRD2/ANKK1 TaqIA polymorphism might contribute to TS susceptibility, especially in Caucasian population. However, further investigation with a larger number of worldwide studies should be conducted to verify the association.
Highlights
Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder with an estimated prevalence of 0.1–1% in children and adolescents from 5 to 18 years old [1]
Combined analysis revealed that the overall odds ratios (ORs) for the Dopamine receptor D2 (DRD2)/ANKK1 TaqIA A1 allele were 1.69 (95%confidence intervals (CIs) = 1.42-2.00) in the fixed-effect model and 1.66 (95%CIs = 1.33-2.08) in the random-effects model
Stratification by ethnicity indicated the TaqIA A1 allele was significantly associated with TS in Caucasians
Summary
Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder with an estimated prevalence of 0.1–1% in children and adolescents from 5 to 18 years old [1]. Positive association results between TS and some of these genes involved in dopaminergic neurotransmission have been reported [12,13,14,15]. Among these genes, dopamine receptor D2 (DRD2) gene, encoding a G protein-coupled receptor located on dopaminergic neurons, is one of the most extensively studied genes in the pathogenesis of TS. Evidence from animal study demonstrated that Ningdong granule effectively inhibited the symptoms of the patients with TS by promoting dopamine metabolism, reducing dopamine levels and mRNA expression of DRD2 in the striatum [15]. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS
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