title: Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease.
abstract: OBJECTIVE
  To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD).
  
  
  METHODS
  A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects.
  
  
  METHODS
  The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany.
  
  
  METHODS
  Five hundred seventeen patients with AD and 390 control subjects.
  
  
  METHODS
  Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects.
  
  
  RESULTS
  Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival.
  
  
  CONCLUSIONS
  CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.
authors.affiliation: Division of Psychiatry Research, University of Zurich, August Forel Str 1, 8008 Zurich, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Finckh
authors.forename: H
authors.initials: H
authors.lastname: von der Kammer
authors.forename: J
authors.initials: J
authors.lastname: Velden
authors.forename: T
authors.initials: T
authors.lastname: Michel
authors.forename: B
authors.initials: B
authors.lastname: Andresen
authors.forename: A
authors.initials: A
authors.lastname: Deng
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Müller-Thomsen
authors.forename: K
authors.initials: K
authors.lastname: Zuchowski
authors.forename: G
authors.initials: G
authors.lastname: Menzer
authors.forename: U
authors.initials: U
authors.lastname: Mann
authors.forename: A
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: R
authors.initials: R
authors.lastname: Heun
authors.forename: J
authors.initials: J
authors.lastname: Zurdel
authors.forename: F
authors.initials: F
authors.lastname: Holst
authors.forename: L
authors.initials: L
authors.lastname: Benussi
authors.forename: G
authors.initials: G
authors.lastname: Stoppe
authors.forename: J
authors.initials: J
authors.lastname: Reiss
authors.forename: A R
authors.initials: AR
authors.lastname: Miserez
authors.forename: H B
authors.initials: HB
authors.lastname: Staehelin
authors.forename: G W
authors.initials: GW
authors.lastname: Rebeck
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
authors.forename: G
authors.initials: G
authors.lastname: Binetti
authors.forename: C
authors.initials: C
authors.lastname: Hock
authors.forename: J H
authors.initials: JH
authors.lastname: Growdon
authors.forename: R M
authors.initials: RM
authors.lastname: Nitsch
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D001057:Apolipoproteins E; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins