The 10-Repeat 3'-UTR VNTR Polymorphism in the <i>SLC6A3</i> Gene May Confer Protection Against Parkinson's Disease: A Meta-analysis.

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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.

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