title: Polymorphisms of the interleukin-1beta gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro.
abstract: OBJECTIVE
  To investigate the role of interleukin-1beta (IL-1beta) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age.
  
  
  RESULTS
  A total of 406 patients with myocardial infarction (MI) at young age, frequency-matched for age, sex, and recruitment center, with 419 healthy population-based controls and 134 patients with ischemic stroke at young age, matched by age and sex, with 134 healthy population-based controls, were studied. Subjects carrying the TT genotype of the -511C/T IL-1beta polymorphism showed a decreased risk of MI (odds ratio [OR], 0.36; 95% CI, 0.20 to 0.64) and stroke (OR, 0.32; 95% CI, 0.13 to 0.81) after adjustment for conventional risk factors. In both studies, the T allele showed a codominant effect (P=0.0020 in MI; P=0.021 in stroke). Mononuclear cells from volunteers carrying the T allele showed a decreased release of IL-1beta and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1beta during cell stimulation resulted in a marked reduction of tissue factor activity expression.
  
  
  CONCLUSIONS
  -511C/T IL-1beta gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.
authors.affiliation: Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy. licia.iacoviello@rm.unicatt.it
authors.forename: L
authors.initials: L
authors.lastname: Iacoviello
authors.forename: A
authors.initials: A
authors.lastname: Di Castelnuovo
authors.forename: M
authors.initials: M
authors.lastname: Gattone
authors.forename: A
authors.initials: A
authors.lastname: Pezzini
authors.forename: D
authors.initials: D
authors.lastname: Assanelli
authors.forename: R
authors.initials: R
authors.lastname: Lorenzet
authors.forename: E
authors.initials: E
authors.lastname: Del Zotto
authors.forename: M
authors.initials: M
authors.lastname: Colombo
authors.forename: E
authors.initials: E
authors.lastname: Napoleone
authors.forename: C
authors.initials: C
authors.lastname: Amore
authors.forename: A
authors.initials: A
authors.lastname: D'Orazio
authors.forename: A
authors.initials: A
authors.lastname: Padovani
authors.forename: G
authors.initials: G
authors.lastname: de Gaetano
authors.forename: P
authors.initials: P
authors.lastname: Giannuzzi
authors.forename: M B
authors.initials: MB
authors.lastname: Donati
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003596:Cytosine / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015810:Linkage Disequilibrium / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*; D013925:Thromboplastin; D013941:Thymine / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D003596:Cytosine; D013925:Thromboplastin; D013941:Thymine