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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:222.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Polymorphisms of the Interleukin-1ß Gene Affect the Risk of Myocardial Infarction and Ischemic Stroke at Young Age and the Response of Mononuclear Cells to Stimulation In Vitro

L. Iacoviello; A. Di Castelnuovo; M. Gattone; A. Pezzini; D. Assanelli; R. Lorenzet; E. Del Zotto; M. Colombo; E. Napoleone; C. Amore; A. D’Orazio; A. Padovani; G. de Gaetano; P. Giannuzzi; M.B. Donati on behalf of IGIGI Investigators

From the Center for High Technology Research and Education in Biomedical Sciences (L.I., A.D., G.d.G., M.B.D.), Catholic University, Campobasso, Italy; Fondazione Salvatore Maugeri (M.G., M.C., P.G.), Clinica del Lavoro e della Riabilitazione, IRCCS, Veruno, Italy; Clinica Neurologica (A. Pezzini, E.D., A. Padovani) and Clinica Cardiologica (D.A.), Università degli Studi di Brescia, Brescia, Italy; and Consorzio Mario Negri Sud (R.L., E.N., C.A., A.D.), Santa Maria Imbaro, Italy.

Correspondence to Licia Iacoviello, MD, PhD, Catholic University, Località Tappino, 86100 Campobasso, Italy. E-mail licia.iacoviello{at}rm.unicatt.it

Objectives— To investigate the role of interleukin-1ß (IL-1ß) 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-1ß 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-1ß and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1ß during cell stimulation resulted in a marked reduction of tissue factor activity expression.

Conclusions— -511C/T IL-1ß gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.

The T allele of the –511C/T polymorphism of the IL-1ß gene reduced the risk of premature MI and stroke. Mononuclear cells from carriers of the T allele showed decreased IL-1ß release and TF expression. Our findings support a role of inflammation in the pathogenesis of ischemic vascular disease.

Key Words: risk factors • genetics • stroke • myocardial infarction • inflammation • coagulation

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