Abstract

The dopamine transporter (DAT) is encoded by the SLC6A3 gene and plays an important role in the regulation of the neurotransmitter dopamine. The SLC6A3 gene contains several repetition alleles (3–11 repeats) of a 40-base pair variable number of tandem repeats (VNTR) in the 3′-untranslated region (3′-UTR), which may affect DAT expression levels. The 10-repeat (10R) allele could play a protective role against PD. However, inconsistent findings have been reported. Methods: A comprehensive meta-analysis was performed to accurately estimate the association between the 10R allele of the 3′-UTR VNTR in SLC6A3 and PD among four different genetic models. Results: This meta-analysis included a total of 3,142 patients and 3,496 controls. We observed a significant difference between patients and controls for the allele model (10R vs. all others: OR = 0.860, 95% CI: 0.771–0.958, P = 0.006), pseudodominant model (10R/10R + 10R/9R vs. all others: OR = 0.781, 95% CI: 0.641–0.952, P = 0.014) and pseudorecessive model (10R/10R vs. all others: OR = 0.858, 95% CI: 0.760–0.969, P = 0.013) using a fixed effects model. No significant differences were observed under the pseudocodominant model (10R/9R vs. all others: OR = 1.079, 95% CI: 0.945–1.233, P = 0.262). By subgroup analysis, the 10R, 10R/10R and 10R/9R genotypes were found to be significantly different from PD in Asian populations. Conclusion: Our findings suggest that the SLC6A3 10R may be a protective factor in susceptibility to PD.

Highlights

  • Specialty section: This article was submitted to Statistical Genetics and Methodology, a section of the journal

  • Our findings suggest that the SLC6A3 10R may be a protective factor in susceptibility to Parkinson’s disease (PD)

  • The remaining 52 articles were evaluated by full-text reading, 34 of which were excluded because 10 were not case-control or cohort studies, 20 were not related to the SLC6A3 3′-untranslated region (3′-UTR) variable number of tandem repeats (VNTR)

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Summary

Introduction

Specialty section: This article was submitted to Statistical Genetics and Methodology, a section of the journal. The dopamine transporter (DAT) is encoded by the SLC6A3 gene and plays an important role in the regulation of the neurotransmitter dopamine. The SLC6A3 gene contains several repetition alleles (3–11 repeats) of a 40-base pair variable number of tandem repeats (VNTR) in the 3′-untranslated region (3′-UTR), which may affect DAT expression levels. The. 10-repeat (10R) allele could play a protective role against PD.

Methods
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