Sequence Variants in SLC6A3, DRD2, and BDNF Genes and Time to Levodopa-Induced Dyskinesias in Parkinson’s Disease

Abstract

Levodopa-induced dyskinesias (LID) present a common but elusive complication of levodopa therapy in Parkinson’s disease (PD). In order to identify genetic factors associated with LID, 352 (213 males) levodopa-treated Israeli PD patients were genotyped for 34 polymorphisms within three candidate genes affecting dopaminergic activity and synaptic plasticity: dopamine transporter gene (DAT1 or SLC6A3) [14 single nucleotide polymorphisms (SNPs) and 40-bp variable number tandem repeat (VNTR)], DRD2 [11 SNPs and dinucleotide CA short tandem repeat (STR)], and BDNF (7 SNPs). A comparison of patients with and without LID was performed by applying a time-oriented approach, with survival analyses evaluating LID development hazard rate over time [Cox proportional hazards and accelerated failure time (AFT) lognormal models]. Overall, 192 (54.5 %) participants developed LID, with a mean latency of 5.0 (±4.5) years. After adjusting for gender, age at PD onset, duration of symptoms prior to levodopa exposure, and multiple testing correction, one SNP in SLC6A3 (with 81 % genotyping success) was significantly associated with LID latency: the C allele of the rs393795 extended the time to LID onset, time ratio = 4.96 (95 % CI, 2.3–10.9; p = 4.1 × 10−5). This finding should be validated in larger, ethnically diverse PD populations, and the biological mechanism should be explored.

DOI: 10.1007/s12031-014-0276-9

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@article{Kaplan2014SequenceVI, title={Sequence Variants in SLC6A3, DRD2, and BDNF Genes and Time to Levodopa-Induced Dyskinesias in Parkinson’s Disease}, author={Natalie Kaplan and Aya Vituri and Amos D. Korczyn and Oren S. Cohen and Rivka Inzelberg and Gilad Yahalom and Evgenia Kozlova and Roni Milgrom and Yael Laitman and Eitan Friedman and Saharon Rosset and Sharon Hassin-Baer}, journal={Journal of Molecular Neuroscience}, year={2014}, volume={53}, pages={183-188} }