A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer’s disease
- 26 September 2000
- journal article
- Published by Wolters Kluwer Health in Neurology
- Vol. 55 (6) , 763-768
- https://doi.org/10.1212/wnl.55.6.763
Abstract
Objective: To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD. Design: A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls. Results: The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE ε4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset. Conclusion: The reduced or absent risk for AD conferred by APOE in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author’s dataset the opposite effects of APOE and CST3 genotype on risk for AD with increasing age suggest that CST3 is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.Keywords
This publication has 36 references indexed in Scilit:
- Butyrylcholinesterase K variant is genetically associated with late onset Alzheimer's disease in Northern IrelandJournal of Medical Genetics, 2000
- No genetic association between polymorphisms in the Tau gene and Alzheimer's disease in clinic or population based samplesNeuroscience Letters, 1999
- The butyrylcholinesterase K variant and susceptibility to Alzheimer's disease.Journal of Medical Genetics, 1998
- The prevalence of apoE-epsilon 4 in Alzheimer's disease is age dependentJournal of Neurology, Neurosurgery & Psychiatry, 1998
- Dietary fat intake and the risk of incident dementia in the Rotterdam studyAnnals of Neurology, 1997
- APOE-??4 in Patients with Alzheimer Disease and Vascular DementiaAlzheimer Disease & Associated Disorders, 1996
- Genetic association of the very low density lipoprotein (VLDL) receptor gene with sporadic Alzheimer's diseaseNature Genetics, 1995
- A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphismNature Genetics, 1995
- Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases.The Journal of Experimental Medicine, 1989
- Hereditary cystatin C (γ-trace) amyloid angiopathy of the CNS causing cerebral hemorrhageActa Neurologica Scandinavica, 1987