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

被引:58
作者
Antonicelli, R
Olivieri, F
Bonafè, M
Cavallone, L
Spazzafumo, L
Marchegiani, F
Cardelli, M
Recanatini, A
Testarmata, P
Boemi, M
Parati, G
Franceschi, C
机构
[1] Italian Natl Res Ctr Aging, Ctr Mol Biol, Ctr Stat, Dept Cardiol, I-60121 Ancona, Italy
[2] Italian Natl Res Ctr Aging, Diabetol Unit, I-60121 Ancona, Italy
[3] Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy
[4] Univ Milan, Dept Clin Med, Milan, Italy
[5] S Luca Hosp, Ist Auxol Italiano, Cardiol Unit 2, Milan, Italy
[6] Univ Bologna, CIG, Interdipartimental Ctr L Galvani, Bologna, Italy
关键词
IL-6; polymorphism; TNF-alpha polymorphism; acute coronary syndrome; inflammation;
D O I
10.1016/j.ijcard.2004.08.064
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
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 >= 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. (c) 2005 Elsevier Ireland Ltd. All. rights reserved.
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收藏
页码:266 / 271
页数:6
相关论文
共 34 条
[1]
Myocardial infarction redefined -: A consensus Document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction [J].
Alpert, JS ;
Antman, E ;
Apple, F ;
Armstrong, PW ;
Bassand, JP ;
de Luna, AB ;
Beller, G ;
Breithardt, G ;
Chaitman, BR ;
Clemmensen, P ;
Falk, E ;
Fishbein, MC ;
Galvani, M ;
Garson, A ;
Grines, C ;
Hamm, C ;
Jaffe, A ;
Katus, H ;
Kjekshus, J ;
Klein, W ;
Klootwijk, P ;
Lenfant, C ;
Levy, D ;
Levy, RI ;
Luepker, R ;
Marcus, F ;
Näslund, U ;
Ohman, M ;
Pahlm, O ;
Poole-Wilson, P ;
Popp, R ;
Alto, P ;
Pyörälä, K ;
Ravkilde, J ;
Rehnquist, N ;
Roberts, W ;
Roberts, R ;
Roelandt, J ;
Rydén, L ;
Sans, S ;
Simoons, ML ;
Thygesen, K ;
Tunstall-Pedoe, H ;
Underwood, R ;
Uretsky, BF ;
Van de Werf, F ;
Voipio-Pulkki, LM ;
Wagner, G ;
Wallentin, L ;
Wijns, W .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2000, 36 (03) :959-969
[2]
Interleukin-6 -174G>C polymorphism and risk of coronary heart disease in West of Scotland Coronary Prevention Study (WOSCOPS) [J].
Basso, F ;
Lowe, GDO ;
Rumley, A ;
McMahon, AD ;
Humphries, SE .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (04) :599-604
[3]
Prognostic value of plasma interleukin-6 concentrations and the -174 G>C and -572 G>C promoter polymorphisms of the interleukin-6 gene in patients with acute myocardial infarction treated with thrombolysis [J].
Bennermo, M ;
Held, C ;
Green, F ;
Strandberg, LE ;
Ericsson, CG ;
Hansson, LO ;
Watkins, H ;
Hamsten, A ;
Tornvall, P .
ATHEROSCLEROSIS, 2004, 174 (01) :157-163
[4]
ATHEROSCLEROSIS - BASIC MECHANISMS - OXIDATION, INFLAMMATION, AND GENETICS [J].
BERLINER, JA ;
NAVAB, M ;
FOGELMAN, AM ;
FRANK, JS ;
DEMER, LL ;
EDWARDS, PA ;
WATSON, AD ;
LUSIS, AJ .
CIRCULATION, 1995, 91 (09) :2488-2496
[5]
Elevated levels of interleukin-6 in unstable angina [J].
Biasucci, LM ;
Vitelli, A ;
Liuzzo, G ;
Altamura, S ;
Caligiuri, G ;
Monaco, C ;
Rebuzzi, AG ;
Ciliberto, G ;
Maseri, A .
CIRCULATION, 1996, 94 (05) :874-877
[6]
Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events [J].
Biasucci, LM ;
Liuzzo, G ;
Fantuzzi, G ;
Caligiuri, G ;
Rebuzzi, AG ;
Ginnetti, F ;
Dinarello, CA ;
Maseri, A .
CIRCULATION, 1999, 99 (16) :2079-2084
[7]
Bonafè M, 2001, EUR J IMMUNOL, V31, P2357, DOI 10.1002/1521-4141(200108)31:8<2357::AID-IMMU2357>3.3.CO
[8]
2-O
[9]
ROLE OF INFLAMMATION IN CORONARY PLAQUE DISRUPTION [J].
BUJA, LM ;
WILLERSON, JT .
CIRCULATION, 1994, 89 (01) :503-505
[10]
Inflammatory markers and onset of cardiovascular events - Results from the Health ABC study [J].
Cesari, M ;
Penninx, BWJH ;
Newman, AB ;
Kritchevsky, SB ;
Nicklas, BJ ;
Sutton-Tyrrell, K ;
Rubin, SM ;
Ding, JZ ;
Simonsick, EM ;
Harris, TB ;
Pahor, M .
CIRCULATION, 2003, 108 (19) :2317-2322