Open Access Highly Accessed Research article

Effect of the G-308A polymorphism of the tumor necrosis factor (TNF)-α gene promoter site on plasma levels of TNF-α and C-reactive protein in smokers: a cross-sectional study

Marie-Louise Gander12, Joachim E Fischer2, Friedrich E Maly3 and Roland von Känel12*

Author Affiliations

1 Department of General Internal Medicine, University Hospital, Bern, Switzerland

2 Institute for Behavioral Sciences, Federal Institute of Technology, Zürich, Switzerland

3 Institute of Clinical Chemistry, University Hospital Zürich, Switzerland

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BMC Cardiovascular Disorders 2004, 4:17  doi:10.1186/1471-2261-4-17

Published: 14 October 2004



Plasma levels of tumor necrosis factor (TNF)-α and of C-reactive protein (CRP) are elevated in smokers. Previous studies failed to show an association between the G-308A polymorphism in the promoter region of the TNF-α gene and coronary artery disease (CAD). We investigated whether smoking would interact with the TNF-α G-308A polymorphism in determining plasma levels of TNF-α and CRP.


Study participants with a complete data set in terms of smoking and the TNF-α G-308A polymorphism were 300 middle-aged male and female industrial employees. After excluding 24 irregular smokers, analyses were performed on 198 "non-smokers" (life-long non-smokers or subjects who quit smoking >6 months ago) as compared to 78 "regular smokers" (subjects currently smoking >3 cigarettes/day). All subjects had a fasting morning blood draw to measure plasma levels of TNF-α and CRP by high-sensitive enzyme-linked immunosorbent assays.


The cardiovascular risk factor adjusted analysis regressing log-transformed CRP levels against smoking status, genotype, and smoking-status-genotype interaction revealed a significant main effect for smoking status (F1,250 = 5.67, p = .018) but not for genotype (F1,250 = 0.33, p = .57). The interaction-term between genotype and smoking status was not significant (F1,250 = 0.09, p = .76). The fully adjusted model with plasma TNF-α failed to show significant main effects for smoking and genotype, as well as for the smoking-status-genotype interaction.


The findings suggest that the TNF-α G-308A polymorphism does not mediate the effect of smoking on plasma CRP levels. It remains to be seen whether other genetic polymorphisms along the inflammatory pathway may modulate vascular risk in smokers.