title: Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders.
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.
authors.affiliation: Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.|Institut für Humangenetik, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Schulte
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Altmaier
authors.affiliation: Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.|Institut für Humangenetik, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Hannah S
authors.initials: HS
authors.lastname: Berger
authors.affiliation: Institute of Computational Biology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Kieu Trinh
authors.initials: KT
authors.lastname: Do
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Wahl
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, 85764, Neuherberg, Germany.|Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: Institute of Computational Biology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Krumsiek
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, PO Box 24144, Doha, Qatar.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haslinger
authors.affiliation: Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.|Schön Klinik München Schwabing, Munich, Germany.
authors.forename: Andres
authors.initials: A
authors.lastname: Ceballos-Baumann
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675, Munich, Germany.|Institut für Humangenetik, Helmholtz Zentrum München, 85764, Neuherberg, Germany.|Institut für Humangenetik, Technische Universität München, 81675, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.|Department of Neurology and Neurosciences, Stanford University, Palo Alto, CA, 94304, United States of America.
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
mesh_terms: D000368:Aged; D002849:Chromatography, Gas; D002853:Chromatography, Liquid; D004298:Dopamine / Q000097:blood* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood* / Q000378:metabolism*; D012148:Restless Legs Syndrome / Q000097:blood* / Q000378:metabolism*
chemical_list: D004298:Dopamine
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