Interleukin-1 Receptor Antagonist Gene Polymorphism and Susceptibility to Ischemic Stroke

Abstract

Cytokines gene polymorphisms have been implicated in susceptibility to ischemic stroke. This study aims to determine the influence of the polymorphism within the intron 2 of the interleukin- 1 receptor antagonist (IL-1Ra) gene on the susceptibility to stroke. A variable number of tandem repeats (VNTR) in intron 2 of the IL-1Ra gene was analyzed in 148 patients with stroke and 161 healthy volunteers from the same area. The carriage rate of allele 2 of IL-1Ra gene, low producer, was significantly higher in patients with stroke compared to the controls (29% vs 21% p = 0.02). Frequency of IL1RN1/IL1RN1 genotype in the patients was significantly lower than the controls (49% vs 66% p = 0.003). The distribution of homozygous genotypes of IL1RN2 was not different between the controls and stroke patients while the heterozygous genotype was more frequent among the patients. (39% vs 25%, respectively). Multiple logistic regression analysis demonstrated that individuals who carry allele 2 for IL-1Ra gene had a significantly higher risk for ischemic stroke with an odds ratio of 2.48 (95% CI, 1.67, 3.51, p = 0.006). These data suggest that allele 2 of the IL-1Ra intron 2 gene represents a susceptibility factor in the development of ischemic stroke.

Influence of IL-1RN Intron 2 Variable Number of Tandem Repeats (VNTR) Polymorphism on Bipolar Disorder

“…This hypothesis is in line with other studies which reported not only a close association of IL1RN*2 allele with severe clinical outcome in chronic inflammatory diseases [38,39], but also supported a role of this polymorphic allele in determining the genetic susceptibility to progressive brain changes that might occur over time during the illness. Supporting this speculation are in vitro studies demonstrating that high IL-1β concentrations can decrease neuronal survival and may promote the neurodegeneration observed in schizophrenia [5,30,40].…”

Polymorphisms of interleukin-1 and interleukin-6 genes on the risk of ischemic stroke in a meta-analysis

“…Four studies were hospital-based case-controls studies (Chamorro et al, 2005;Dziedzic et al, 2005;Flex et al, 2004;Um et al, 2003a), thirteen studies were population-based case-control studies, and one study (Worrall et al, 2007) did not report the source of controls. All of the studies were in goodness-in-fitness of HWE except for three studies (Lee et al, 2010;Li et al, 2010;Rezaii et al, 2009).…”

“…In total, twenty case-control studies in seventeen articles (Balding et al, 2004;Banerjee et al, 2008;Chamorro et al, 2005;Dziedzic et al, 2005;Flex et al, 2004;Iacoviello et al, 2005;Lai et al, 2006;Lalouschek et al, 2006;Lee et al, 2010;Li et al, 2010;Rezaii et al, 2009;Rubattu et al, 2005;Seripa et al, 2003;Tong et al, 2010;Um et al, 2003a;Worrall et al, 2007;Zee et al, 2008) were included in this meta-analysis. Of these studies, five studies (Lai et al, 2006;Lee et al, 2004;Li et al, 2010;Tong et al, 2010;Um et al, 2003a) were for Asians, one study (Worrall et al, 2007) was for American Africans, and the other studies were for Caucasians.…”

“…Through four steps, i.e., reviewing titles, abstracts, full texts and browsing reference lists of eligible studies and relevant review papers, eligible studies were identified. In total, three case-control studies with 864 cases and 1223 controls for IL1α-889C/T (Banerjee et al, 2008;Li et al, 2010;Um et al, 2003a), eight studies with 1434 cases and 1594 controls for IL1β-511C/T (Dziedzic et al, 2005;Iacoviello et al, 2005;Lai et al, 2006;Li et al, 2010;Rubattu et al, 2005;Seripa et al, 2003;Zee et al, 2008), eight studies with 1423 cases and 1729 controls for IL1-Ra (Balding et al, 2004;Lai et al, 2006;Lee et al, 2010;Rezaii et al, 2009;Seripa et al, 2003;Um et al, 2003a;Worrall et al, 2007) and seven studies with 1879 cases and 2092 controls for IL6-147G/C (Balding et al, 2004;Banerjee et al, 2008;Chamorro et al, 2005;Flex et al, 2004;Lalouschek et al, 2006;Tong et al, 2010) were included in this meta-analysis.…”

Interleukin-1 and Stroke: Biomarker, Harbinger of Damage, and Therapeutic Target

“…Inhibition of the neuronal NLRP1 inflammasome (which is involved in the processing and release of IL-1 through the activation of caspase-1) improves outcome after stroke, traumatic or spinal cord injury [19,20,21]. Further support for a role for IL-1 in stroke comes from the observations that IL-1 or IL-1Ra gene polymorphisms are associated with altered susceptibility to stroke, carotid atherosclerosis and intracranial haemorrhage in humans [22,23,24,25,26,27]. …”