title: D2 dopamine receptor A1 allele in Alzheimer disease and aging.
abstract: BACKGROUND
  The apolipoprotein E4 (APOE*4) allele is a major risk factor for the common forms of late-onset Alzheimer disease (AD), but does not account for all the genetic variation in late-onset AD; hence, other genetic markers must be examined. The D2 dopamine receptor (DRD2) A1 allele is associated with abnormal brain function and decreased DRD2s. These receptors are decreased in hippocampus and amygdala in AD, and allele frequencies may vary with age.
  
  
  OBJECTIVE
  To study APOE and DRD2 genotypes in patients with AD and cognitively intact controls of varying ages.
  
  
  METHODS
  The DRD2 and APOE genotypes were examined in 832 unrelated white subjects, including 554 patients with AD (486 sporadic; 68 familial) and 278 controls. Logistic regressions tested A1 allele effects on disease status and age, and DRD2 linkage with AD was investigated in 60 families with late-onset AD.
  
  
  METHODS
  University medical centers.
  
  
  METHODS
  Patients (mean +/- SD age, 74.6 +/- 8.1 years; range, 52-98 years) had probable AD, according to standard consensus diagnostic criteria; controls (mean +/- SD age, 69.2 +/- 8.6 years; range, 50-93 years) were cognitively intact.
  
  
  METHODS
  Disease status, age, and DRD2 linkage with AD.
  
  
  RESULTS
  No association between the DRD2 and APOE alleles was found, and the presence of the A1 allele did not increase the risk for AD. There was also no evidence of linkage between DRD2 and AD. Age analyses, including both patients and controls, indicated a decrease in A1 allele frequency with age.
  
  
  CONCLUSIONS
  The A1 allele does not contribute to AD risk, alone or in combination with the APOE*4 allele. The DRD2 A1 allele frequencies decrease with age in both patients and controls. Thus, studies of DRD2 disease association need to control for age.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine; VA Medical Center, West Los Angeles, Calif, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Small
authors.forename: E P
authors.initials: EP
authors.lastname: Noble
authors.forename: S S
authors.initials: SS
authors.lastname: Matsuyama
authors.forename: L F
authors.initials: LF
authors.lastname: Jarvik
authors.forename: S
authors.initials: S
authors.lastname: Komo
authors.forename: A
authors.initials: A
authors.lastname: Kaplan
authors.forename: T
authors.initials: T
authors.lastname: Ritchie
authors.forename: M L
authors.initials: ML
authors.lastname: Pritchard
authors.forename: A M
authors.initials: AM
authors.lastname: Saunders
authors.forename: P M
authors.initials: PM
authors.lastname: Conneally
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics*; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D017448:Receptors, Dopamine D2