The effect of the Interleukin‐6–174G > C promoter gene polymorphism on endothelial function in healthy volunteers

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Abstract
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.