Abstract | BACKGROUND:
C-reactive protein (CRP) plays a major role in the immune system and is an independent risk marker of cardiovascular disease. However, CRP's role in atherogenesis as innocent bystander, causative, or even protective agent, remains unresolved. The (+)1444C/T alteration in the CRP gene has been reported to determine basal CRP concentrations. We hypothesized that this alteration may also be associated with the degree of inflammatory response and coagulation activation in a well-standardized model of systemic inflammation. METHODS: RESULTS: Basal concentrations of high-sensitivity CRP were approximately 40% lower in (+)1444CC alteration carriers than in T homozygous (TT) allele carriers (P = 0.04). In contrast, basal IL6 concentrations were 2-fold higher in wild-type C homozygous (CC) than in TT individuals (P = 0.01). In response to the LPS challenge, CC individuals had 4-fold higher peak TNFalpha concentrations (P <0.01), >2.5-fold higher peak IL6 concentrations (P <0.01), and increased temperature (P <0.01). Twenty-four hours after LPS challenge, prothrombin fragment F(1+2) concentrations were 75% higher and D-dimer concentrations 50% higher in CC than in TT individuals (P <0.05). CONCLUSIONS: Genetic factors regulating CRP concentrations also modulate the individual response to endotoxin-stimulated inflammation.
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Authors | Claudia Marsik, Raute Sunder-Plassmann, Bernd Jilma, Florian M Kovar, Christine Mannhalter, Oswald Wagner, Helmut Rumpold, Georg Endler |
Journal | Clinical chemistry
(Clin Chem)
Vol. 52
Issue 10
Pg. 1952-7
(Oct 2006)
ISSN: 0009-9147 [Print] England |
PMID | 16916988
(Publication Type: Journal Article)
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Chemical References |
- Fibrin Fibrinogen Degradation Products
- Interleukin-6
- Lipopolysaccharides
- Peptide Fragments
- Tumor Necrosis Factor-alpha
- fibrin fragment D
- prothrombin fragment 1.2
- Prothrombin
- C-Reactive Protein
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Topics |
- Adult
- Blood Coagulation
- C-Reactive Protein
(genetics)
- Endotoxemia
(blood, immunology, metabolism)
- Escherichia coli
- Fibrin Fibrinogen Degradation Products
(analysis)
- Genotype
- Humans
- Inflammation
(metabolism)
- Interleukin-6
(blood)
- Lipopolysaccharides
(pharmacology)
- Male
- Mutation
- Peptide Fragments
(analysis)
- Polymerase Chain Reaction
- Prothrombin
(analysis)
- Tumor Necrosis Factor-alpha
(analysis)
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