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PLoS One. 2016 Jan 25;11(1):e0147129. doi: 10.1371/journal.pone.0147129. eCollection 2016.

Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders.

Author information

1
Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.
2
Institut für Humangenetik, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
3
Institute of Genetic Epidemiology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
4
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
5
Institute of Computational Biology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
6
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
7
Institute of Epidemiology II, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
8
Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
9
Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
10
Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, PO Box 24144, Doha, Qatar.
11
Schön Klinik München Schwabing, Munich, Germany.
12
Institut für Humangenetik, Technische Universität München, 81675, Munich, Germany.
13
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
14
Department of Neurology and Neurosciences, Stanford University, Palo Alto, CA, 94304, United States of America.

Abstract

BACKGROUND:

Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS) and Parkinson`s disease (PD) represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases.

METHODS:

456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls.

RESULTS:

After stringent quality control, we identified decreased levels of long-chain (polyunsaturated) fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9) and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32). In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7). The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD.

CONCLUSIONS:

A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention.

PMID:
26808974
PMCID:
PMC4726488
DOI:
10.1371/journal.pone.0147129
[Indexed for MEDLINE]
Free PMC Article

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