The effect of the Interleukin-6-174G > C promoter gene polymorphism on endothelial function in healthy volunteers.
Brull DJ., Leeson CPM., Montgomery HE., Mullen M., deDivitiis M., Humphries SE., Deanfield JE.
AIMS: Atherosclerosis is a chronic inflammatory condition, manifest in its early stages by endothelial dysfunction. Interleukin-6 (IL6) plays a key role in driving this process through stimulation of acute phase protein synthesis. We have examined the effect of the IL6 gene -174G > C promoter polymorphism on endothelial function in a group of healthy subjects. METHODS: 248 adults aged 20-28 years participated. Polymerase chain reaction was performed for the -174G > C polymorphism. Brachial artery diameter was measured at rest and after forearm cuff occlusion by high-resolution ultrasound. Responses were represented as absolute flow mediated dilatation (FMDA). RESULTS: Overall there was a trend towards greater FMDA for genotype CC, P = 0.14. No effect was seen in women; however, in men, following multivariate analysis, there was a significant association between genotype and FMDA, P = 0.04. In addition, a significant detrimental effect of smoking on FMDA was only seen in males of genotype CC (P < 0.05) when compared to nonsmokers of the same genotype. CONCLUSION: IL6-174G > C promoter polymorphism influences endothelial function in healthy male subjects. The detrimental effect of smoking on endothelial function is most clearly seen in men of genotype -174 CC, suggesting a genotype-specific interaction with smoking.