title: Clinical and biochemical differences in patients having Parkinson disease with vs without GBA mutations.
abstract: OBJECTIVE
  Biochemical abnormalities present in GBA (mut/wt) carriers may offer new pathogenetic insights to and potential therapeutic targets in Parkinson disease (PD).
  
  
  OBJECTIVE
  To determine whether patients having PD with vs without GBA mutations differ in clinical phenotype or plasma protein expression.
  
  
  METHODS
  Case-control study of patients having PD with vs without GBA mutations. Clinical characteristics were compared between groups, and biochemical profiling of 40 plasma proteins was performed to identify proteins that differed in expression between groups.
  
  
  METHODS
  The discovery cohort included 20 patients having PD with GBA mutations. Clinical characteristics of GBA-associated PD cases were compared with those of 242 patients having PD in whom GBA mutations were excluded by full gene sequencing.
  
  
  METHODS
  Biochemical profiling was available for all 20 GBA-associated PD cases, as well as a subset (87 of 242) of the GBA-negative PD cases. The replication cohort included 19 patients having PD with GBA mutations and 41 patients having PD without GBA mutations.
  
  
  RESULTS
  Compared with patients having PD without GBA mutations, patients having PD with GBA mutations were younger at disease onset (P = .04) and were more likely to demonstrate cognitive dysfunction (P = .001). In a multiple regression model that included age, sex, and assay batch as covariates, GBA mutation status was significantly associated with plasma levels of interleukin 8 (P = .001), monocyte chemotactic protein 1 (P = .008), and macrophage inflammatory protein 1α (P = .005). The association between interleukin 8 and GBA mutation status was replicated (P = .03) in a separate cohort of patients having PD with vs without GBA mutations.
  
  
  CONCLUSIONS
  Patients having PD with GBA mutations have earlier age at disease onset and are more likely to demonstrate cognitive dysfunction. Monocyte-associated inflammatory mediators may be elevated in patients having PD with GBA mutations.
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: Lama M
authors.initials: LM
authors.lastname: Chahine
authors.forename: Judy
authors.initials: J
authors.lastname: Qiang
authors.forename: Emily
authors.initials: E
authors.lastname: Ashbridge
authors.forename: James
authors.initials: J
authors.lastname: Minger
authors.forename: Dora
authors.initials: D
authors.lastname: Yearout
authors.forename: Stacy
authors.initials: S
authors.lastname: Horn
authors.forename: Amy
authors.initials: A
authors.lastname: Colcher
authors.forename: Howard I
authors.initials: HI
authors.lastname: Hurtig
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: Vivianna M
authors.initials: VM
authors.lastname: Van Deerlin
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Siderowf
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: Alice
authors.initials: A
authors.lastname: Chen-Plotkin
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D010641:Phenotype; D001617:beta-Glucosidase / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*
chemical_list: D001798:Blood Proteins; D001617:beta-Glucosidase