Abstract 3937: Effect of the 252A>G Polymorphism of the Lymphotoxin-α Gene on Inflammatory Markers of Response to Cigarette Smoking in Korean Healthy Men
The systemic inflammatory response is heightened in smokers. This study examined whether the established cardiovascular risk factor, smoking status, might interact with the lymphotoxin-α (LTA) 252A>G gene polymorphism in determining serum levels of TNF-α and eventually IL-6, adiponectin and CRP downstream in the inflammatory cascade. After adjustment for age, 208 smokers with an average consumption of 18±1 cigarettes/d had higher levels of TNF-α, IL-6, CRP and urinary excretion of 8-epi PGF2α than nonsmokers (n=272). Nonsmokers with G/G (n=58) had higher concentrations of TNF-α and 8-epi PGF2α than those with A/A (n=90) or A/G (n=124). TNF-α concentrations were higher in smokers than nonsmokers of the same genotype. Smokers with G/G (n=36) showed higher concentrations of TNF-α than those with A/A (n=65). Smokers with G/G had higher levels of circulating IL-6 and urinary 8-epi PGF2α than those with A/G (n=107) or A/A. Furthermore, smokers with A/G or G/G showed lower adiponectin concentrations than those with A/A. The adjusted model TNF-α levels showed main effects of genotype (F=4.897, P=0.028) and for smoking (F=7.240, P=0.001), as well as the smoking status-genotype interaction (F=3.882, P=0.001). TNF-α concentrations had a positive relation with serum concentrations of IL-6 (r=0.385, P<0.001) and a negative relation with adiponectin (r=-0.123, P<0.05). In conclusion, our results suggest that LTA 252A>G polymorphism may modulate the inflammatory effects and oxidative stress of smoking in healthy men. The detrimental effect of smoking on inflammatory markers and oxidative stress is most clearly seen in men of genotype 252G/G, suggesting a genotype-specific interaction with smoking.