title: SLC6A3 is a risk factor for Parkinson's disease: a meta-analysis of sixteen years' studies.
abstract: The human dopamine transporter gene (gene symbol: SLC6A3) is considered as a candidate risk factor for Parkinson's disease because dopamine transporter accumulates cytotoxic dopamine or other toxins in the dopamine neurons. However, findings from numerous association studies in different populations have been inconsistent with each other. In this study, we performed a combined analysis of published case-control genetic association data between SLC6A3 and Parkinson's disease. The results indicate that SLC6A3 confers a modest but significant risk for Parkinson's disease in various populations. Allele 10-repeat of the 40-base pair variable number tandem repeat, a well studied polymorphism in the 3' untranslated region of SLC6A3, confers neuroprotection in East Asian (OR: 0.78, 95% CI: 0.65, 0.94 and p=0.009) but not in Caucasian populations. Genotype GG and allele G of the promoter single nucleotide polymorphism rs2652510 is associated with a risk in Caucasians (allelic G, OR: 1.26, 95% CI: 1.04-1.54, and p=0.018; genotypic GG OR: 1.37, 95% CI: 1.03-1.84 and p=0.032). Such information implies a population-dependent involvement of SLC6A3 in the etiology of Parkinson's disease.
authors.affiliation: Department of Public Health, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Zhai
authors.affiliation: School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Songji
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China; Department of Psychiatry and Harvard NeuroDiscovery Center, Harvard Medical School and Laboratory of Psychiatric Neurogenomics, Division of Alcohol and Drug Abuse, McLean Hospital, Belmont, MA 02478, USA. Electronic address: zhaoyingxxmc@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Psychiatry and Harvard NeuroDiscovery Center, Harvard Medical School and Laboratory of Psychiatric Neurogenomics, Division of Alcohol and Drug Abuse, McLean Hospital, Belmont, MA 02478, USA. Electronic address: zhicheng_lin@hms.harvard.edu.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lin
mesh_terms: D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*; D012307:Risk Factors
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human
keywords: Dopamine transporter; Genetic etiology; Neurodegeneration; Parkinson's disease; Polymorphism