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Elevated white cell count in acute coronary syndromes: relationship to variants in inflammatory and thrombotic genes.

Byrne CE, Fitzgerald A, Cannon CP, Fitzgerald DJ, Shields DC - BMC Med. Genet. (2004)

Bottom Line: We sought to identify whether pro-inflammatory genetic variants contributed to alterations in WBC and C-reactive protein (CRP) in an ACS population.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).Cytokine pro-inflammatory genetic variants do not influence the increased inflammatory profile of ACS patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. cbyrne@rcsi.ie

ABSTRACT

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.

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Platelet count (cells/mm3) versus IL1RN and IL-6 genotypes for the (a) OPUS TIMI-16, (b) Platelet count (109/L) EXCITE stable angina and (c) Platelet count (109/L) EXCITE ACS patient groups. See Fig. 1 for details.
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Figure 2: Platelet count (cells/mm3) versus IL1RN and IL-6 genotypes for the (a) OPUS TIMI-16, (b) Platelet count (109/L) EXCITE stable angina and (c) Platelet count (109/L) EXCITE ACS patient groups. See Fig. 1 for details.

Mentions: Secondary analyses investigated the impact of the pro-inflammatory gene variants on other inflammatory markers and on troponin. Platelet count did not significantly differ according to IL-6 genotype (Fig. 2a). However, the IL1RN*2/*2 homozygote was associated with a reduced platelet count. This was nominally significant (p = 0.002), and after correction for 4 pro-inflammatory genotypes and the 4 measures investigated this finding remains of borderline significance (16 tests, corrected p = 0.03). No associations were found between the genotypes and CRP, β-fibrinogen or troponin levels (Figure 3a,3b,3c).


Elevated white cell count in acute coronary syndromes: relationship to variants in inflammatory and thrombotic genes.

Byrne CE, Fitzgerald A, Cannon CP, Fitzgerald DJ, Shields DC - BMC Med. Genet. (2004)

Platelet count (cells/mm3) versus IL1RN and IL-6 genotypes for the (a) OPUS TIMI-16, (b) Platelet count (109/L) EXCITE stable angina and (c) Platelet count (109/L) EXCITE ACS patient groups. See Fig. 1 for details.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC425582&req=5

Figure 2: Platelet count (cells/mm3) versus IL1RN and IL-6 genotypes for the (a) OPUS TIMI-16, (b) Platelet count (109/L) EXCITE stable angina and (c) Platelet count (109/L) EXCITE ACS patient groups. See Fig. 1 for details.
Mentions: Secondary analyses investigated the impact of the pro-inflammatory gene variants on other inflammatory markers and on troponin. Platelet count did not significantly differ according to IL-6 genotype (Fig. 2a). However, the IL1RN*2/*2 homozygote was associated with a reduced platelet count. This was nominally significant (p = 0.002), and after correction for 4 pro-inflammatory genotypes and the 4 measures investigated this finding remains of borderline significance (16 tests, corrected p = 0.03). No associations were found between the genotypes and CRP, β-fibrinogen or troponin levels (Figure 3a,3b,3c).

Bottom Line: We sought to identify whether pro-inflammatory genetic variants contributed to alterations in WBC and C-reactive protein (CRP) in an ACS population.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).Cytokine pro-inflammatory genetic variants do not influence the increased inflammatory profile of ACS patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. cbyrne@rcsi.ie

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus