Kaplan N et al. Sequence variants in SLC6A3, DRD2, and BDNF genes and time to levodopa-induced dyskinesias in Parkinson's disease. J Mol Neurosci. 2014 Jun;53(2):183-8. PMID: 24633632.

J Mol Neurosci. 2014 Jun;53(2):183-8. doi: 10.1007/s12031-014-0276-9. Epub 2014 Mar 15.

Sequence variants in SLC6A3, DRD2, and BDNF genes and time to levodopa-induced dyskinesias in Parkinson's disease.

Kaplan N(1), Vituri A, Korczyn AD, Cohen OS, Inzelberg R, Yahalom G, Kozlova E, Milgrom R, Laitman Y, Friedman E, Rosset S, Hassin-Baer S.

Author information:
(1)The Parkinson Disease and Movement Disorders Clinic, Department of Neurology and Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel Hashomer, 52621, Ramat Gan, Israel.

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.

PMID: 24633632  [PubMed - indexed for MEDLINE]

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