Background and Purpose-Proinflammatory cytokines including interleukin-6 (IL-6) are supposed to play a pivotal role in the development of atherosclerosis. A common polymorphism in the promoter of the IL-6 gene (IL-6 Ϫ174GϾC) affects plasma IL-6 concentrations and has been suggested as a risk factor for cardiovascular disease. The aim of the present case-control study was to investigate the role of this polymorphism for retinal artery occlusion (RAO). Methods-One hundred eighty-two patients with RAO and 307 control subjects were genotyped for the IL-6 Ϫ174GϾC polymorphism. Genotypes were determined by fluorogenic exonuclease (TaqMan) assay. Results-The prevalence of the CC genotype was significantly lower in patients with RAO than in control subjects (10.4% versus 19.9%; Pϭ0.006). Homozygosity for the C allele was associated with an odds ratio of 0.50 (95% CI, 0.28 to 0.89) for RAO. Key Words: atherosclerosis Ⅲ genetics Ⅲ interleukin-6 Ⅲ ophthalmology Ⅲ retinal artery occlusion Ⅲ risk factors A therosclerosis is a low-grade chronic inflammatory disease. 1 Numerous cytokines including interleukin 6 (IL-6) have been suggested to play an essential role in atherogenesis. 2 IL-6 is a pleiotropic cytokine and is synthesized by several different cell types, including monocytes and vascular endothelial cells. 3 Immunohistochemical studies found both increased IL-6 protein and mRNA concentrations in atherosclerotic plaques. 4 -6 Further evidence for its role in atherogenesis comes from animal experiments, showing that IL-6 promotes the development of early atherosclerotic lesions. 7 In humans, increased plasma IL-6 levels have been associated with unstable angina and have predicted future cardiovascular events. 8 -12 In 1998, a functional polymorphism in the promoter region of the IL-6 gene at position Ϫ174 (Ϫ174GϾC) was identified. 13 An in vitro study using transfected human cell line cells reported higher baseline IL-6 levels in cells with the G construct compared with those transfected with the C allele. 13 Stimulation with lipopolysaccharides or IL-1 resulted in a significantly increased IL-6 transcription rate; this effect, however, was restricted to cells with the G allele. In another in vitro study using anti-CD3/CD28 -stimulated peripheral blood lymphocytes, IL-6 concentrations were 3ϫ higher among carriers of the G allele. 14 Additionally, some but not all in vivo studies found higher plasma IL-6 concentrations in subjects with the GG genotype than among homozygotes for the C allele. 13,15,16 Recently, the Ϫ174GϾC gene polymorphism has been suggested as a risk factor for coronary heart disease, carotid atherosclerosis and stroke. [17][18][19][20][21][22][23][24][25] Its role in retinal artery occlusion (RAO), however, has not yet been determined.
Conclusions-TheRAO is a common cause for a severe visual loss in patients Ͼ50 years. Impaired blood flow in the central retinal artery or one of its branches leads to infarction of the affected retinal tissue. Embolization and hemorrhage under an atherosclerotic pla...