The interleukin-6 -174 G>C promoter polymorphism is associated with a higher risk of death after an acute coronary syndrome in male elderly patients.
BACKGROUND
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are key mediators of inflammation and their increased plasma levels are associated with acute coronary syndrome (ACS). Polymorphisms in the promoter region of IL-6 (-174 G>C) and TNF-alpha (-308 G>A) demonstrated to affect gene expression were analyzed to test their predictive power for cardiovascular death over one year follow-up in elderly male ACS patients.


METHODS
We assessed the IL-6 -174 G>C polymorphism and TNF-alpha -308 G>A polymorphism in 139 consecutive elderly male patients affected by an ACS, such as ST-Elevation (STEMI), No ST-Elevation (NSTEMI) Myocardial Infarction and Unstable Angina. The presence of well known risk factors for Coronary Heart Diseases (CHD) were also assessed in all ACS patients. Survival rate was assessed after one year follow-up.


RESULTS
We found that IL-6 -174 G>C polymorphism is an independent predictor of cardiovascular death after an ACS in male patients. In particular ACS patients carrying the IL-6 -174 C- (GG) genotypes showed a marked increase in one year follow-up mortality rate (HR=3.89, 95% CI 1.71-8.86, p=0.001). Moreover CRP serum levels > or = 5.5 mg/dl (HR= 3.79, 95% CI 1.71-8.42, p=0.001), a history of CHD (HR=2.96, 95% CI 1.22-7.20, p=0.016) and the absence of statins treatment (HR=3.27, 95% CI 1.17-9.18, p=0.021), significantly increased one year risk of death in male ACS patients.


CONCLUSIONS
These data suggest that IL-6 -174 G>C polymorphism can be added to other clinical markers in order to identify a subgroup of elderly ACS male patients at higher risk of death.
Antonicelli
Roberto
R
Department of Cardiology, Center of Molecular Biology, Center of Statistics and Diabetologic Unit, Italian National Research Centers on Aging (INRCA), Via della Montagnola, 81, 60121 Ancona, Italy. r.antonicelli@inrca.it
Olivieri
Fabiola
F
Bonafè
Massimiliano
M
Cavallone
Luca
L
Spazzafumo
Liana
L
Marchegiani
Francesca
F
Cardelli
Maurizio
M
Recanatini
Andrea
A
Testarmata
Paolo
P
Boemi
Massimo
M
Parati
Gianfranco
G
Franceschi
Claudio
C
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D005819:Genetic Markers; D006801:Humans; D015850:Interleukin-6; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D005819:Genetic Markers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha