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.

Type

Journal article

Journal

Eur J Clin Invest

Publication Date

03/2002

Volume

32

Pages

153 - 157

Keywords

Adult, Arteriosclerosis, Brachial Artery, Endothelium, Vascular, Female, Genotype, Humans, Interleukin-6, Male, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Risk Factors, Sex Distribution, Smoking