Effect of the 252A>G polymorphism of the lymphotoxin-alpha 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-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.
Jang
Yangsoo
Y
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]
Koh
Soo Jeong
SJ
Kim
Oh Yoen
OY
Kim
Byoung-Keuk
BK
Choi
Donghoon
D
Hyun
Yae Jung
YJ
Kim
Hyae Jin
HJ
Chae
Jey Sook
JS
Lee
Jong Ho
JH
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*
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D018836:Inflammation Mediators; D008233:Lymphotoxin-alpha; D006151:Guanosine; D000241:Adenosine