Interaction between smoking and the interleukin-6 gene affects systemic levels of inflammatory biomarkers.
BACKGROUND
Smoking is associated with a systemic inflammatory response. However, the role of genetic predisposition is not well known. We assessed whether circulatory acute phase reactants were associated with smoking and whether or not the association was modified by the major cytokine gene of the acute phase reaction, interleukin-6 (IL-6).


METHODS
In total, 1,003 postmyocardial infarction patients were recruited in six European cities and six repeated clinical examinations performed. C-reactive protein (CRP), interleukin 6 (IL-6), and fibrinogen levels were assayed at 5,659 subject visits. Genotyping of single nucleotide polymorphisms was performed in the IL-6 gene.


RESULTS
Cumulative smoking (pack-years) and time since smoking cessation were strongly associated with blood levels of all three inflammatory markers. Among subjects without any respiratory disorder, these associations remained statistically significant for CRP and IL-6. A polymorphism in the IL-6 gene (rs2069840) showed an interaction with smoking on CRP (p < .001) and IL-6 (p = .049) peripheral levels.


CONCLUSIONS
These results indicate a potential role of the IL-6 gene in the inflammatory response associated with smoking and suggest rs2069840 polymorphism deserves attention.
Sunyer
Jordi
J
Centre for Environmental Epidemiological Research, Dr. Aiguader 88, 08003 Barcelona, Spain. jsunyer@imim.es
Forastiere
F
F
Pekkanen
J
J
Plana
E
E
Kolz
M
M
Pistelli
R
R
Jacquemin
B
B
Brüske-Hohlfeld
I
I
Pitsavos
Ch
Ch
Bellander
T
T
Koenig
W
W
Peters
A
A
D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000502:physiology; D012907:Smoking / Q000097:blood* / Q000235:genetics*
D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein