Elevated white cell count in acute coronary syndromes: relationship to variants in inflammatory and thrombotic genes.
BACKGROUND
Elevated white blood cell counts (WBC) in acute coronary syndromes (ACS) increase the risk of recurrent events, but it is not known if this is exacerbated by pro-inflammatory factors. We sought to identify whether pro-inflammatory genetic variants contributed to alterations in WBC and C-reactive protein (CRP) in an ACS population.


METHODS
WBC and genotype of interleukin 6 (IL-6 G-174C) and of interleukin-1 receptor antagonist (IL1RN intronic repeat polymorphism) were investigated in 732 Caucasian patients with ACS in the OPUS-TIMI-16 trial. Samples for measurement of WBC and inflammatory factors were taken at baseline, i.e. Within 72 hours of an acute myocardial infarction or an unstable angina event.


RESULTS
An increased white blood cell count (WBC) was associated with an increased C-reactive protein (r = 0.23, p < 0.001) and there was also a positive correlation between levels of beta-fibrinogen and C-reactive protein (r = 0.42, p < 0.0001). IL1RN and IL6 genotypes had no significant impact upon WBC. The difference in median WBC between the two homozygote IL6 genotypes was 0.21/mm3 (95% CI = -0.41, 0.77), and -0.03/mm3 (95% CI = -0.55, 0.86) for IL1RN. Moreover, the composite endpoint was not significantly affected by an interaction between WBC and the IL1 (p = 0.61) or IL6 (p = 0.48) genotype.


CONCLUSIONS
Cytokine pro-inflammatory genetic variants do not influence the increased inflammatory profile of ACS patients.
Byrne
Connie E
CE
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. cbyrne@rcsi.ie
Fitzgerald
Anthony
A
Cannon
Christopher P
CP
Fitzgerald
Desmond J
DJ
Shields
Denis C
DC
D000208:Acute Disease; D000789:Angina, Unstable / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002986:Clinical Trials as Topic; D003328:Coronary Thrombosis / Q000235:genetics; D005340:Fibrinogen / Q000032:analysis; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000235:genetics; D007958:Leukocyte Count; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D012008:Recurrence; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics; D013577:Syndrome
D015415:Biomarkers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D012795:Sialoglycoproteins; D005340:Fibrinogen; D002097:C-Reactive Protein