TY - JOUR
T1 - Polymorphisms of the interleukin-1β gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro
AU - Iacoviello, Licia
AU - Di Castelnuovo, A.
AU - Gattone, M.
AU - Pezzini, A.
AU - Assanelli, D.
AU - Lorenzet, R.
AU - Del Zotto, E.
AU - Colombo, M.
AU - Napoleone, E.
AU - Amore, C.
AU - D'Orazio, A.
AU - Padovani, A.
AU - De Gaetano, G.
AU - Giannuzzi, P.
AU - Donati, M. B.
PY - 2005/1
Y1 - 2005/1
N2 - Objectives - To investigate the role of interleukin-1β (IL-1β) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age. Methods and 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-1β 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-1β and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1β during cell stimulation resulted in a marked reduction of tissue factor activity expression. Conclusions - 511C/T IL-1β gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.
AB - Objectives - To investigate the role of interleukin-1β (IL-1β) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age. Methods and 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-1β 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-1β and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1β during cell stimulation resulted in a marked reduction of tissue factor activity expression. Conclusions - 511C/T IL-1β gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.
KW - Coagulation
KW - Genetics
KW - Inflammation
KW - Myocardial infarction
KW - Risk factors
KW - Stroke
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U2 - 10.1161/01.ATV.0000150039.60906.02
DO - 10.1161/01.ATV.0000150039.60906.02
M3 - Article
C2 - 15539626
AN - SCOPUS:19944427889
VL - 25
SP - 222
EP - 227
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 1
ER -