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

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.

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-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.