Effect of the 252A>G polymorphism of the lymphotoxin-α gene on inflammatory markers of response to cigarette smoking in Korean healthy men

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 PGF_2α 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 PGF_2α than nonsmokers (n = 272). Nonsmokers with G/G had higher TNF-α and 8-epi PGF_2α 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 PGF_2α 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.