TY - JOUR
T1 - Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease
AU - Finckh, Ulrich
AU - Von Der Kammer, Heinz
AU - Velden, Joachim
AU - Michel, Tiana
AU - Andresen, Barbara
AU - Deng, Amy
AU - Zhang, Jun
AU - Müller-Thomsen, Tomas
AU - Zuchowski, Kathrin
AU - Menzer, Gunnar
AU - Mann, Ulrike
AU - Papassotiropoulos, Andreas
AU - Heun, Reinhard
AU - Zurdel, Jan
AU - Holst, Frederik
AU - Benussi, Luisa
AU - Stoppe, Gabriela
AU - Reiss, Jochen
AU - Miserez, André R.
AU - Staehelin, Hannes B.
AU - Rebeck, G. William
AU - Hyman, Bradley T.
AU - Binetti, Giuliano
AU - Hock, Christoph
AU - Growdon, John H.
AU - Nitsch, Roger M.
PY - 2000
Y1 - 2000
N2 - Objective: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). Design: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. Setting: 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. Participants: Five hundred seventeen patients with AD and 390 control subjects. Measures: Molecular testing of the Kspl 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 ε4; 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.
AB - Objective: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). Design: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. Setting: 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. Participants: Five hundred seventeen patients with AD and 390 control subjects. Measures: Molecular testing of the Kspl 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 ε4; 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.
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M3 - Article
C2 - 11074789
AN - SCOPUS:0033733370
VL - 57
SP - 1579
EP - 1583
JO - Archives of Neurology
JF - Archives of Neurology
SN - 0003-9942
IS - 11
ER -