Association between DRD2/ANKK1 TaqIA Polymorphism and Susceptibility with Tourette Syndrome: A Meta-Analysis

Aihua Yuan; Liang Su; Shunying Yu; Chunbo Li; Tao Yu; Jinhua Sun

doi:10.1371/journal.pone.0131060

Association between DRD2/ANKK1 TaqIA Polymorphism and Susceptibility with Tourette Syndrome: A Meta-Analysis

PLoS One. 2015 Jun 25;10(6):e0131060. doi: 10.1371/journal.pone.0131060. eCollection 2015.

Authors

Aihua Yuan¹, Liang Su², Shunying Yu³, Chunbo Li², Tao Yu⁴, Jinhua Sun⁵

Affiliations

¹ Department of Genetics, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Center for Translational Neuromedicine and the Department of Neurology, University of Rochester Medical Center, Rochester, New York, United States of America.
² Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Genetics, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Medical Psychology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China; Department of Child & Adolescent Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: Genetic 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.

Methods: Literature 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.

Results: 523 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.

Conclusions: This 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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Asian People / genetics
Case-Control Studies
Genetic Predisposition to Disease / genetics*
Genotype
Humans
Polymorphism, Genetic / genetics*
Protein Serine-Threonine Kinases / genetics*
Receptors, Dopamine D2 / genetics*
Risk
Tourette Syndrome / etiology
Tourette Syndrome / genetics*
White People / genetics

Substances

DRD2 protein, human
Receptors, Dopamine D2
ANKK1 protein, human
Protein Serine-Threonine Kinases

Grants and funding

The study was supported by grants from the National Natural Science Foundation of China (81301146) (http://www.nsfc.gov.cn/; discussion about the data and results) and the Shanghai Natural Science Foundation (10ZR1425600, 12ZR1427000, 14ZR1435800) (http://www.stcsm.gov.cn/; data collection). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.