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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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Related in: MedlinePlus

For each of the IL1RN and IL-6 genotypes patients the median (central line) is shown. Flanking this is a dark shaded box, representing the 95% confidence interval of the median. This gives an indication of the confidence in the estimate of the median. The white boxes represent the inter-quartile range (from 25th percentile to the 75th percentile), giving an indication of the variability in WBC among patients. (a) WBC (cells/mm3) OPUS TIMI-16 ACS patients (b) WBC (109/L) EXCITE stable angina and (c) WBC (109/L) EXCITE ACS patient groups.
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Figure 1: For each of the IL1RN and IL-6 genotypes patients the median (central line) is shown. Flanking this is a dark shaded box, representing the 95% confidence interval of the median. This gives an indication of the confidence in the estimate of the median. The white boxes represent the inter-quartile range (from 25th percentile to the 75th percentile), giving an indication of the variability in WBC among patients. (a) WBC (cells/mm3) OPUS TIMI-16 ACS patients (b) WBC (109/L) EXCITE stable angina and (c) WBC (109/L) EXCITE ACS patient groups.

Mentions: The primary hypothesis that we sought to address was whether the white cell counts of ACS patients were significantly influenced by pro-inflammatory genotype. Fig. 1a indicates that the white cell counts were not influenced by either the IL1RN or their IL6 genotypes. The difference in median WBC between the two homozygote IL6 genotypes was 0.21/mm3 (95% CI = -0.41 to 0.77), representing only 6.3% of the inter-quartile range of WBC. The difference in median WBC between the two homozygote IL1RN genotypes was -0.03/mm3 (95% CI = -0.55 to 0.86), representing only 0.9% of the inter-quartile range. Given the relative rarity of the *2/*2 genotype, we compared the IL1RN*1/*1 and *1/*2 genotypes, who differ in median by -0.23/mm3 (95% CI = -0.64 to 0.24) or just 6.8% of the interquartile range.


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)

For each of the IL1RN and IL-6 genotypes patients the median (central line) is shown. Flanking this is a dark shaded box, representing the 95% confidence interval of the median. This gives an indication of the confidence in the estimate of the median. The white boxes represent the inter-quartile range (from 25th percentile to the 75th percentile), giving an indication of the variability in WBC among patients. (a) WBC (cells/mm3) OPUS TIMI-16 ACS patients (b) WBC (109/L) EXCITE stable angina and (c) WBC (109/L) EXCITE ACS patient groups.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: For each of the IL1RN and IL-6 genotypes patients the median (central line) is shown. Flanking this is a dark shaded box, representing the 95% confidence interval of the median. This gives an indication of the confidence in the estimate of the median. The white boxes represent the inter-quartile range (from 25th percentile to the 75th percentile), giving an indication of the variability in WBC among patients. (a) WBC (cells/mm3) OPUS TIMI-16 ACS patients (b) WBC (109/L) EXCITE stable angina and (c) WBC (109/L) EXCITE ACS patient groups.
Mentions: The primary hypothesis that we sought to address was whether the white cell counts of ACS patients were significantly influenced by pro-inflammatory genotype. Fig. 1a indicates that the white cell counts were not influenced by either the IL1RN or their IL6 genotypes. The difference in median WBC between the two homozygote IL6 genotypes was 0.21/mm3 (95% CI = -0.41 to 0.77), representing only 6.3% of the inter-quartile range of WBC. The difference in median WBC between the two homozygote IL1RN genotypes was -0.03/mm3 (95% CI = -0.55 to 0.86), representing only 0.9% of the inter-quartile range. Given the relative rarity of the *2/*2 genotype, we compared the IL1RN*1/*1 and *1/*2 genotypes, who differ in median by -0.23/mm3 (95% CI = -0.64 to 0.24) or just 6.8% of the interquartile range.

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