Background: The systemic inflammatory response is heightened in smokers. We examined whether the established cardiovascular risk factor, smoking status, might interact with the lymphotoxin-α (LTA) gene 252A>G polymorphism in determining concentrations of TNF-α and eventually IL-6, adiponectin and CRP downstream in the inflammatory cascade. Methods: We measured anthropometric parameters, serum lipid profile, glucose, TNF-α, IL-6, CRP, adiponectin and urinary excretion of 8-epi PGF2α as well as a genotyping for 252A>G polymorphism of LTA in 480 healthy Korean men. Results: After adjustment for age, 208 smokers with an average consumption of 18 ± 1 cigarettes/d had higher concentrations of TNF-α, IL-6, CRP and urinary excretion of 8-epi PGF2α than nonsmokers (n = 272). Nonsmokers with G/G had higher TNF-α and 8-epi PGF2α concentrations than those with A/A or A/G. TNF-α concentrations were higher in smokers than nonsmokers of the same genotype. Smokers with G/G showed higher TNF-α concentration than those with A/A and had higher IL-6 and urinary 8-epi PGF2α concentrations than those with A/G or A/A. Furthermore, smokers carrying the G allele showed lower adiponectin concentrations than those with A/A. There are main effects of genotype and smoking, as well as the smoking-genotype interaction to TNF-α concentration. Conclusion: Our results suggest that the LTA 252A>G polymorphism may modulate the inflammatory effects and oxidative stress of smoking. The detrimental effect of smoking is most clearly seen in men with G/G, suggesting a genotype-specific interaction with smoking.
Bibliographical noteFunding Information:
We sincerely thank study participants and the support of 1) National Research Laboratory project #2005-01572, Ministry of Science and Technology, Seoul, Korea 2) Korea Health 21 R&D Projects, Ministry of Health and Welfare, Seoul, Korea (A000386, A020593) 3) Yonsei Biomedical Science and Technology Initiative (YBSTI) program and 4) Brain Korea 21 Project, Yonsei University College of Human Ecology, Brain Korea 21 Project for Medical Science, Yonsei University.
All Science Journal Classification (ASJC) codes
- Clinical Biochemistry
- Biochemistry, medical