Interleukin-6 −174G/C Polymorphism and Ischemic Stroke

Abstract

Background and Purpose-Interleukin-6 (IL-6) is associated with atherosclerotic disease and is also a key mediator in the inflammatory response to cerebral ischemia. Although the IL-6 Ϫ174G/C promoter polymorphism has been associated with carotid artery atherosclerosis and coronary heart disease, its relation to ischemic stroke is unclear. This review summarizes the current literature and discusses methodological considerations for future studies. Methods-Electronic searches were conducted in the PubMed MEDLINE, Scopus, and ISI Web of Science databases. Two investigators independently reviewed all abstracts to identify studies examining the association between the IL-6 Ϫ174G/C polymorphism and ischemic cerebrovascular events. Results-Twelve relevant publications were identified. Three reported on a subset of patients from a later publication, leaving 9 independent studies. Two studies found an association between ischemic stroke and the G allele or GG genotype, whereas 4 found an association with the C allele or CC genotype. One study found the CC genotype to be significantly less frequent in retinal artery occlusion patients. Two studies found no association between the Ϫ174G/C polymorphism and stroke. Conclusions-Studies investigating stroke and the Ϫ174G/C polymorphism report conflicting results, which may reflect the complex physiology of IL-6 and true differences between stroke subtypes and populations. However, interpretation of published results is hindered by methodological limitations, and greater rigor and consistency in future studies will help unravel the relationship between the Ϫ174G/C polymorphism and stroke. (Stroke.

Genetics of stroke

“…Elevated plasma levels of IL-6 are associated with an increased risk and worse outcome of acute vascular events. A common G/C promoter polymorphism in the IL-6 gene has been shown to affect basal IL-6 levels, with the C allele associated with lower plasma IL-6 levels [32] . However, epidemiological data on the association of the IL-6 gene polymorphism with ischemic stroke, subtypes and intermediate phenotypes are conflicting.…”

Association of variable number of tandem repeat polymorphism in the IL-4 gene with ischemic stroke in the Chinese Uyghur population

“…Susceptibility to infection/inflammation and/or risk of atherosclerosis and IS events were shown to be associated with genetic variations in genes and cytokine receptor genes (Worrall et al, 2003;Markus et al, 2006;Steinbrugger et al, 2009). However, data relating these inflammatory cytokine polymorphisms to cerebrovascular events are absent or debatable (Lalouschek et al, 2006;Tso et al, 2007;Yamada et al, 2008).…”

The Impact of Inflammation on Cognitive Impairment in Chronic Kidney Disease Patients

“…These authors [43] found that IL-6 deficiency induces a distracting effect in the recognition memory of this kind of mice. A systematic review by Tso et al [44], where studies that examined the relation between IL-6 and the IL-6 -174G/C polymorphism, supported that IL-6 elevated levels are associated with a higher risk of stroke. However, there are conflicting results in the literature and it remains unclear whether an association between the IL-6 -174G/C polymorphism and the ischemic cerebrovascular events exists, due to the complexity of the IL-6 physiology [44].…”