title: Association of Parkinson disease age of onset with DRD2, DRD3 and GRIN2B polymorphisms.
abstract: BACKGROUND
  Dopamine and glutamate are crucial neurotransmitters in Parkinson disease (PD). While recent large meta-analyses reported that genetic variation of dopamine (DRD2, DRD3) and glutamine (NMDA, GRIN2B) neurotransmitter receptors was not associated with PD risk, they could conceivably influence PD phenotype. We studied the association of these receptor polymorphisms relating to PD age of onset.
  
  
  METHODS
  There were 664 PD patients and 718 controls, all Caucasian, with stored DNA at Mayo Clinic, Jacksonville, Florida. Genotyping was performed for DRD2 (Taq 1A, rs1800497), DRD3 (rs6280), and NMDA (GRIN2B, rs7301328) polymorphisms with ABI Taqman assays. Single nucleotide polymorphism associations with age of onset were evaluated using dominant, recessive, and additive genotypic models.
  
  
  RESULTS
  DRD3 variant carriers had an approximate 4.4-year decrease in mean age of onset when both copies of the minor allele were present (P = 0.0034) and an approximate 1.5-year decrease in mean age at onset for every additional minor allele (P = 0.023) (recessive and additive models, respectively). There was no association with age of onset for DRD2 or GRIN2B under any statistical model (all P ≥ 0.22).
  
  
  CONCLUSIONS
  The DRD3 (rs6280) polymorphism, but not DRD2 (Taq1A) or GRIN2B, influences younger PD age of onset in the US Caucasian population. Validation of these findings in larger studies with other ethnic groups is indicated.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address: hassan.anhar@mayo.edu.
authors.forename: Anhar
authors.initials: A
authors.lastname: Hassan
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Heckman
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Ahlskog
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Serie
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Jay A
authors.initials: JA
authors.lastname: van Gerpen
authors.affiliation: Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neuroscience, University of Florida, Gainesville, FL, USA.
authors.forename: Sruti
authors.initials: S
authors.lastname: Rayaprolu
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; C493593:DRD3 protein, human; C121001:NR2B NMDA receptor; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Age; Dopamine; Genetics; NMDA; Parkinsonism; Receptor