Genetic variation in the interleukin-6 gene in relation to risk and outcomes in acute coronary syndrome.
BACKGROUND
The concept of inflammation in the acute coronary syndrome (ACS) is today well established. Interleukin-6 (IL-6), a pleiotropic, proinflammatory cytokine, seems to play an important role in the development and progression of ACS.


OBJECTIVE
The aim was to investigate whether IL6 polymorphisms are associated with patient/control status, outcome in patients with ACS and plasma concentrations of IL-6 and C-reactive protein (CRP).


METHODS
Samples for citrated plasma and DNA were obtained on admission from 3027 patients with non-ST-elevation ACS in the FRISC-II study. A group of 447 healthy controls of similar age and gender as the patients was also recruited. Eight IL6 polymorphisms were genotyped and plasma concentrations of IL-6 and CRP measured in patients and controls.


RESULTS
No associations between patient/control status, clinical outcome, ST-depression, troponin-T elevation or a history of myocardial infarction and IL6 polymorphisms were observed. In the full patient group, there was a trend towards association of the -572 G>C polymorphism with plasma concentrations of IL-6 (p=0.07). This association was statistically significant in patients with available high-sensitivity measurements of IL-6 (p=0.01). The -572 CG genotype was predictive for IL-6 levels above 5 ng/L in patients with a subsequent cardiovascular event, 2.3 (1.1-4.3) (adjusted odds ratio, 95% confidence interval). Comparison with data from HapMap showed that our panel of polymorphisms covered information on approximately 30 other IL6 variants.


CONCLUSIONS
The -572 G>C and other polymorphisms in the study were not associated with outcome in ACS patients. However, the -572 CG genotype may contribute to a more distinct inflammatory response in patients with ACS.
Mälarstig
Anders
A
Department of Medical Sciences, Clinical Chemistry, Uppsala University, S-751 85 Uppsala, Sweden.
Wallentin
Lars
L
Siegbahn
Agneta
A
D000208:Acute Disease; D000925:Anticoagulants / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D017985:Dalteparin / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000925:Anticoagulants; D015850:Interleukin-6; D002097:C-Reactive Protein; D017985:Dalteparin