title: Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington's disease peripheral blood samples.
abstract: BACKGROUND
  Metabolic changes have been frequently associated with Huntington's disease (HD). At the same time peripheral blood represents a minimally invasive sampling avenue with little distress to Huntington's disease patients especially when brain or other tissue samples are difficult to collect.
  
  
  OBJECTIVE
  We investigated the levels of 163 metabolites in HD patient and control serum samples in order to identify disease related changes. Additionally, we integrated the metabolomics data with our previously published next generation sequencing-based gene expression data from the same patients in order to interconnect the metabolomics changes with transcriptional alterations.
  
  
  METHODS
  This analysis was performed using targeted metabolomics and flow injection electrospray ionization tandem mass spectrometry in 133 serum samples from 97 Huntington's disease patients (29 pre-symptomatic and 68 symptomatic) and 36 controls.
  
  
  RESULTS
  By comparing HD mutation carriers with controls we identified 3 metabolites significantly changed in HD (serine and threonine and one phosphatidylcholine-PC ae C36:0) and an additional 8 phosphatidylcholines (PC aa C38:6, PC aa C36:0, PC ae C38:0, PC aa C38:0, PC ae C38:6, PC ae C42:0, PC aa C36:5 and PC ae C36:0) that exhibited a significant association with disease severity. Using workflow based exploitation of pathway databases and by integrating our metabolomics data with our gene expression data from the same patients we identified 4 deregulated phosphatidylcholine metabolism related genes (ALDH1B1,MBOAT1,MTRRandPLB1) that showed significant association with the changes in metabolite concentrations.
  
  
  CONCLUSIONS
  Our results support the notion that phosphatidylcholine metabolism is deregulated in HD blood and that these metabolite alterations are associated with specific gene expression changes.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Mastrokolias
authors.affiliation: Department of Biological Psychology, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, The Netherlands ; The EMGO + Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Rene
authors.initials: R
authors.lastname: Pool
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Eleni
authors.initials: E
authors.lastname: Mina
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Hettne
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, 2300 RC Leiden, The Netherlands ; Center for Mental Health Care Delfland, Jorisweg 2, Delft, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: van Duijn
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Roos C
authors.initials: RC
authors.lastname: van der Mast
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: GertJan
authors.initials: G
authors.lastname: van Ommen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.affiliation: Helmholtz Zentrum, München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: Helmholtz Zentrum, München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany ; German Center for Diabetes Research, Neuherberg, Germany ; Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Willeke
authors.initials: W
authors.lastname: van Roon-Mom
keywords: Biomarkers; Disease progression; Gene expression; Integrated analysis; Metabolomics; Neurodegenerative