Interleukin-1 gene cluster polymorphisms in cerebral infarction

Interleukin-1 (IL-1) has pleiotropic actions in the central nervous system. During the past decade, a growing corpus of evidence has indicated an important role of this cytokine in the development of brain damage following cerebral ischaemia. The expression of IL-1 in the brain is dramatically increased during the early and chronic stage of infarction. The IL-1 gene cluster on chromosome 2ql4 contains three related genes (IL-1alpha, IL-1beta, and IL-1 receptor antagonist, IL-1ra) located within a 430-kb region. Polymorphisms in the genes encoding IL-1alpha, IL-1beta, and IL-1ra have been associated with several inflammatory diseases. Therefore we hypothesized that these cytokines might be good candidates for cerebral infarction (CI). We ascertained these genotypes in 363 CI patients and 640 controls matched for age and gender. A significant increase was found for the IL-1alpha (-889) allele 2 carriers in CI patients compared with controls (chi(2) = 5.633, P = 0.018, odds ratio (OR)=1.5). Furthermore, the IL-1 a (-889) allele 2 carriers increased the relative risk for CI in the subjects without the IL-1ra allele 2 (chi(2) = 7.989, P = 0.005, OR= 1.7). There was no significant association between IL-1beta (+3953) polymorphism and CI. These results suggest that IL-1alpha-889 and IL-1ra polymorphisms are effective in the development of CI in Koreans. (C) 2003 Elsevier Ltd. All rights reserved.