on November 11, 2004
Published online before print November 11, 2004, doi: 10.1161/01.ATV.0000150039.60906.02
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Submitted on September 5, 2004
Accepted on October 21, 2004
Polymorphisms of the Interleukin-1
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 *;
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.
* To whom correspondence should be addressed. E-mail: licia.iacoviello{at}rm.unicatt.it.
Objectives--To investigate the role of interleukin-1
(IL-1) 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-1 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-1 and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1 during cell stimulation resulted in a marked reduction of tissue factor activity expression.
Conclusions---511C/T IL-1 gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.
Key words: risk factors • genetics • stroke • myocardial infarction • inflammation • coagulation
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