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Sharing Pathogenetic Mechanisms between Acute Myocardial Infarction and Alzheimer's Disease as Shown by Partially Overlapping of Gene Variant Profiles

Sharing Pathogenetic Mechanisms between Acute Myocardial Infarction and Alzheimer's Disease as... Gene variants that promote inflammation and cholesterol metabolism have been associated with acute myocardial infarction (AMI) and Alzheimer's disease (AD). We investigated a panel of relevant polymorphisms to distinguish genetic backgrounds for AMI and AD: IL10 −1082G/A, IL6 −174G/C, TNF −308G/A, IFNG +874T/A, SERPINA3 −51G/T, HMGCR −911C/A, APOE ε2/3/4 (280 AMI cases, 257 AD cases, and 1307 population controls, all Italian (presumed risk alleles are shown in bold). Six genetic risk sets I to VI were identified by fuzzy latent classification: I had low risk; II and III had low risk before age 65 (II, III); low risk sets lacked pro-inflammatory alleles for HMGCR-TNF-APOE. Pro-inflammatory alleles for SERPINA3–IL10–IFNG were found for high risk sets IV to VI. Set IV ‘AMI < age 40, AD < age 65’ included risk alleles for HMGCR. Set V ‘AMI over a broad range of age’ included risk alleles for TNF+IL6. Set VI ‘AMI at ages 40 to 55, AD ages 65+’ included APOE ε4. Close resemblance to the high risk sets, as indicated by membership scores close to one, defined high relative risks. We conclude that AMI and AD share genetic backgrounds involving cholesterol metabolism and the upregulation of inflammation and that gene-gene interactions in relevant sets of genes may be useful in defining inherited risk for common disorders. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Alzheimer's Disease IOS Press

Sharing Pathogenetic Mechanisms between Acute Myocardial Infarction and Alzheimer's Disease as Shown by Partially Overlapping of Gene Variant Profiles

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Publisher
IOS Press
Copyright
Copyright © 2011 by IOS Press, Inc
ISSN
1387-2877
eISSN
1875-8908
DOI
10.3233/JAD-2010-090871
pmid
21098980
Publisher site
See Article on Publisher Site

Abstract

Gene variants that promote inflammation and cholesterol metabolism have been associated with acute myocardial infarction (AMI) and Alzheimer's disease (AD). We investigated a panel of relevant polymorphisms to distinguish genetic backgrounds for AMI and AD: IL10 −1082G/A, IL6 −174G/C, TNF −308G/A, IFNG +874T/A, SERPINA3 −51G/T, HMGCR −911C/A, APOE ε2/3/4 (280 AMI cases, 257 AD cases, and 1307 population controls, all Italian (presumed risk alleles are shown in bold). Six genetic risk sets I to VI were identified by fuzzy latent classification: I had low risk; II and III had low risk before age 65 (II, III); low risk sets lacked pro-inflammatory alleles for HMGCR-TNF-APOE. Pro-inflammatory alleles for SERPINA3–IL10–IFNG were found for high risk sets IV to VI. Set IV ‘AMI < age 40, AD < age 65’ included risk alleles for HMGCR. Set V ‘AMI over a broad range of age’ included risk alleles for TNF+IL6. Set VI ‘AMI at ages 40 to 55, AD ages 65+’ included APOE ε4. Close resemblance to the high risk sets, as indicated by membership scores close to one, defined high relative risks. We conclude that AMI and AD share genetic backgrounds involving cholesterol metabolism and the upregulation of inflammation and that gene-gene interactions in relevant sets of genes may be useful in defining inherited risk for common disorders.

Journal

Journal of Alzheimer's Disease – IOS Press

Published: Jan 1, 2011

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