The effect of the Interleukin-6-174G > C promoter gene polymorphism on endothelial function in healthy volunteers.
OBJECTIVE
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.


CONCLUSIONS
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.
Brull
D J
DJ
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Dept. of Medicine, Royal Free and University College London Medical School, Rayne Building, 5 University Street, London WC1E 6JJ, UK. D.Brull@ucl.ac.uk
Leeson
C P M
CP
Montgomery
H E
HE
Mullen
M
M
deDivitiis
M
M
Humphries
S E
SE
Deanfield
J E
JE
Lesson
C P M
CP
D000328:Adult; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D001916:Brachial Artery / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D017678:Sex Distribution; D012907:Smoking
D015850:Interleukin-6