Acute myocardial infarction and proinflammatory gene variants.
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 epsilon2/3/4; 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.
Department of Experimental Pathology, School of Medicine, University of Bologna, Via S. Giacomo 14, Bologna. Italy.
Federico
F
Licastro
Martina
M
Chiapelli
Claudio Marcello
CM
Caldarera
Calogero
C
Caruso
Domenico
D
Lio
Elizabeth H
EH
Corder
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000097:blood / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D015843:Serpins / Q000235:genetics* / Q000378:metabolism
D001057:Apolipoproteins E; D016207:Cytokines; C516148:SERPINA3 protein, human; D015843:Serpins; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases