Sharing pathogenetic mechanisms between acute myocardial infarction and Alzheimer's disease as shown by partially overlapping of gene variant profiles.

6533b86efe1ef96bd12cbe2f

RESEARCH PRODUCT

Sharing pathogenetic mechanisms between acute myocardial infarction and Alzheimer's disease as shown by partially overlapping of gene variant profiles.

Domenico Lio Elizabeth H. Corder Elisa Porcellini Claudio Marcello Caldarera Calogero Caruso Martina Chiappelli Federico Licastro Ilaria Carbone

subject

Apolipoprotein E Adult Male Population Myocardial Infarction Disease Alzheimer Disease Risk Factors Genes Overlapping Medicine Humans Settore MED/05 - Patologia Clinica Genetic Predisposition to Disease Myocardial infarction Allele education genetic risk markers common soil alzheimer disease AMI GOM analysys Gene Aged Genetics Aged 80 and over education.field_of_study business.industry General Neuroscience Gene Expression Profiling Genetic Variation General Medicine Middle Aged medicine.disease Psychiatry and Mental health Clinical Psychology Relative risk Immunology Tumor necrosis factor alpha Female Geriatrics and Gerontology business

description

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 e2/3/4 (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 e4. 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.

year	journal	country	edition	language
2011-01-01

http://hdl.handle.net/10447/74645