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Genetic markers of Restless Legs Syndrome in Parkinson disease.

ABSTRACT: Several studies proposed that Restless Legs Syndrome (RLS) and Parkinson disease (PD) may be clinically and/or etiologically related. To examine this hypothesis, we aimed to determine whether the known RLS genetic markers may be associated with PD risk, as well as with PD subtype.Two case-control cohorts from Tel-Aviv and New-York, including 1133 PD patients and 867 controls were genotyped for four RLS-related SNPs in the genes MEIS1, BTBD9, PTPRD and MAP2K5/SKOR1. The association between genotype, PD risk and phenotype was tested using multivariate regression models.None of the tested SNPs was significantly associated with PD risk, neither in any individual cohort nor in the combined analysis after correction for multiple comparisons. The MAP2K5/SKOR1 marker rs12593813 was associated with higher frequency of tremor in the Tel-Aviv cohort (61.0% vs. 46.5%, p = 0.001, dominant model). However, the risk allele for tremor in this gene has been associated with reduced RLS risk. Moreover, this association did not replicate in Tremor-dominant PD patients from New-York.RLS genetic risk markers are not associated with increased PD risk or subtype in the current study. Together with previous genetic, neuropathological and epidemiologic studies, our results further strengthen the notion that RLS and PD are likely to be distinct entities.

SUBMITTER: Gan-Or Z

PROVIDER: S-EPMC4441838 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Genetic markers of Restless Legs Syndrome in Parkinson disease.

Gan-Or Ziv Z Alcalay Roy N RN Bar-Shira Anat A Leblond Claire S CS Postuma Ronald B RB Ben-Shachar Shay S Waters Cheryl C Johnson Amelie A Levy Oren O Mirelman Anat A Gana-Weisz Mali M Dupré Nicolas N Montplaisir Jacques J Giladi Nir N Fahn Stanley S Xiong Lan L Dion Patrick A PA Orr-Urtreger Avi A Rouleau Guy A GA

Parkinsonism & related disorders 20150317 6

<h4>Introduction</h4>Several studies proposed that Restless Legs Syndrome (RLS) and Parkinson disease (PD) may be clinically and/or etiologically related. To examine this hypothesis, we aimed to determine whether the known RLS genetic markers may be associated with PD risk, as well as with PD subtype.<h4>Methods</h4>Two case-control cohorts from Tel-Aviv and New-York, including 1133 PD patients and 867 controls were genotyped for four RLS-related SNPs in the genes MEIS1, BTBD9, PTPRD and MAP2K5/ ...[more]

PMID: 25817513

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Project description:Study objectivesRestless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data.MethodsOne hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability.ResultsRLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88).ConclusionsRLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.

Dataset Information

Genetic markers of Restless Legs Syndrome in Parkinson disease.

Publications

Genetic markers of Restless Legs Syndrome in Parkinson disease.

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