Interleukin-6 174G/C polymorphism and ischemic stroke: a systematic review.
OBJECTIVE
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 -174G/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 -174G/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 -174G/C polymorphism and stroke.


CONCLUSIONS
Studies investigating stroke and the -174G/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 -174G/C polymorphism and stroke.
Tso
Amy R
AR
National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Dr, Rm B1D733, MSC 1063, Bethesda, MD 20892, USA.
Merino
José G
JG
Warach
Steven
S
D000328:Adult; D002545:Brain Ischemia / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D002648:Child; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D015850:Interleukin-6 / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D015203:Reproducibility of Results; D020521:Stroke / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology
D015850:Interleukin-6