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a Department of Experimental Pathology, School of Medicine, University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy b Istituto Nazionale Ricerche Cardiovascolari, Imola, Italy c Department of Biopathology and Biomedical Methodology, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy d Center for Demographic Studies, 2117 Campus Drive, Duke University, Durham, North Carolina 27708-0408, USA
Key Words: acute myocardial infarction • inflammation • gene variants • grade-of-membership analysis • cholesterol • apolipoprotein E
Address for correspondence: Elizabeth H. Corder, Ph.D., Duke University, Box 90408, Durham, NC 27708-0408. Voice: +1-303-449-2491; fax: +1-303-449-2491. elizabethcorder{at}hotmail.com
We identified four genetic risk sets for acute myocardial infarction (AMI) from information on functional gene variants that favor inflammation or modulate cholesterol metabolism: IL6 -174 G/C, TNF -308 G/A, IL10 -1082 G/A, SERPINA3 -51 G/T, IFNG +874 T/A, HMGCR -911 C/A, and APOE
 2/3/4; 316 patients and 461 healthy subjects, all Italian. Putative risk alleles are shown underlined. The sets were identified using grade-of-membership analysis. Membership scores in the sets are automatically generated for individuals. The ‘low intrinsic risk’ set had alleles that downregulate inflammation and cholesterol synthesis (IL6, TNF, ILl0, HMGCR). ‘AMI across a broad age range’ carried multiple proinflammatory alleles (IL6, TNF, IL10, SERPINA3): All 72 persons like this set were affected yet had relatively low plasma cholesterol levels. ‘A subset of AMI in middle age’ had numerous proinflammatory alleles (IL6, TNF, SERPINA3, IFNG, HMGCR). ‘AMI after age 80’ had a reduced risk set (IL6, IL10, IFNG). A total of 95% of cases had  50% membership in the high intrinsic risk sets. We conclude that proinflammatory gene variants taken together strongly determine an individual's risk for myocardial infarction. This information may better define the pathogenesis of myocardial infarction and identify individuals who might benefit from early interventions.
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