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

Article type: Research Article

Authors: Licastro, Federico^{a; *} | Chiappelli, Martina^a | Caldarera, Claudio Marcello^b | Porcellini, Elisa^a | Carbone, Ilaria^a | Caruso, Calogero^c | Lio, Domenico^c | Corder, Elizabeth H.^d

Affiliations: [a] Department of Experimental Pathology, School of Medicine, University of Bologna, Bologna, Italy | [b] Istituto Nazionale Ricerche Cardiovascolari, Imola, Italy | [c] Department of Biopathology and Biomedical Methodology, University of Palermo, Palermo, Italy | [d] Matrix Genomics, Inc., Santa Fe, NM, USA

Correspondence: [*] Correspondence to: Federico Licastro, MD, Associate Research Professor, Laboratory of Immunopathology and Immunogenetics, Department of Experimental Pathology, University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy. Tel.: +39 051 2094730; Fax: +39 051 2094746; E-mail: [email protected].

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.

Keywords: Acute myocardial infarction, Alzheimer's disease, APOE, cholesterol, gene polymorphism, genetic epidemiology, grade-of-membership analysis, inflammation

DOI: 10.3233/JAD-2010-090871

Journal: Journal of Alzheimer's Disease, vol. 23, no. 3, pp. 421-431, 2011