title: Effect of the 252A>G polymorphism of the lymphotoxin-alpha gene on inflammatory markers of response to cigarette smoking in Korean healthy men.
abstract: BACKGROUND
  The systemic inflammatory response is heightened in smokers. We examined whether the established cardiovascular risk factor, smoking status, might interact with the lymphotoxin-alpha (LTA) gene 252A>G polymorphism in determining concentrations of TNF-alpha and eventually IL-6, adiponectin and CRP downstream in the inflammatory cascade.
  
  
  METHODS
  We measured anthropometric parameters, serum lipid profile, glucose, TNF-alpha, IL-6, CRP, adiponectin and urinary excretion of 8-epi PGF2alpha 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-alpha, IL-6, CRP and urinary excretion of 8-epi PGF2alpha than nonsmokers (n=272). Nonsmokers with G/G had higher TNF-alpha and 8-epi PGF2alpha concentrations than those with A/A or A/G. TNF-alpha concentrations were higher in smokers than nonsmokers of the same genotype. Smokers with G/G showed higher TNF-alpha concentration than those with A/A and had higher IL-6 and urinary 8-epi PGF2alpha 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-alpha concentration.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, and Cardiovascular Center of National Health Insurance Corporation Ilsan Hospital, Koyang, Republic of Korea [corrected]
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Koh
authors.forename: Oh Yoen
authors.initials: OY
authors.lastname: Kim
authors.forename: Byoung-Keuk
authors.initials: BK
authors.lastname: Kim
authors.forename: Donghoon
authors.initials: D
authors.lastname: Choi
authors.forename: Yae Jung
authors.initials: YJ
authors.lastname: Hyun
authors.forename: Hyae Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jey Sook
authors.initials: JS
authors.lastname: Chae
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000241:Adenosine / Q000235:genetics*; D052242:Adiponectin / Q000097:blood; D000328:Adult; D000483:Alleles; D015415:Biomarkers; D005838:Genotype; D006151:Guanosine / Q000235:genetics*; D006262:Health; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D018836:Inflammation Mediators; D008233:Lymphotoxin-alpha; D006151:Guanosine; D000241:Adenosine