Skip to main content

Advertisement

Log in

Genetic polymorphism of the C-reactive protein (CRP) gene and a deep infection focus determine maximal serum CRP level in Staphylococcus aureus bacteremia

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

C-reactive protein (CRP) is widely used in early detection of sepsis or organ dysfunction. Several single nucleotide polymorphisms (SNPs) in the CRP gene are shown to be associated with variability of basal CRP. To clarify the effect of these SNPs to CRP response in systemic infections, we compared genetic and clinical data on patients with Staphylococcus aureus bacteremia (SAB). Six SNPs in the CRP gene region (rs2794521, rs30912449, rs1800947, rs1130864, rs1205 and rs3093075) were genotyped in 145 patients and analyzed for associations with CRP and various clinical outcomes. We found that the rare minor A-allele of triallelic SNP rs30912449 (C > T > A) and presence of a deep infection focus were strongly associated to the higher maximal CRP during the first week of SAB. Median of the maximal CRP in patients who had the A-minor allele was 282 mg/L (interquartile range [IQR, defined as the difference between the third quartile and the first quartile], 169 mg/L) but only 179 mg/L (IQR, 148 mg/L) in patients without this allele (P = 0.004), and CRP in patients who had deep infection focus was higher 208 mg/L (IQR, 147 mg/L) than in other patients 114 mg/L (IQR, 121 mg/l) (P < 0.0001). Mortality, degree of leucocytosis, time to defervescence or number of deep infections were not affected by CRP gene SNPs. The maximal CRP during the first week in SAB was partly determined by variation in the CRP gene and partly by presence of deep infection focus. This finding suggests cautiousness in interpreting exceptionally high CRPs from SAB patients and comparison between patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Black S, Kushner I, Samols D (2004) C-reactive protein. J Biol Chem 279(47):48487–48490

    Article  CAS  PubMed  Google Scholar 

  2. Povoa P (2002) C-reactive protein: a valuable marker of sepsis. Intensive Care Med 28(3):235–243

    Article  PubMed  Google Scholar 

  3. Povoa P, Coelho L, Almeida E et al (2006) Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study. Crit Care 10(2):R63

    Article  PubMed  Google Scholar 

  4. Lobo SM, Lobo FR, Bota DP et al (2003) C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 123(6):2043–2049

    Article  CAS  PubMed  Google Scholar 

  5. Agrawal A, Suresh MV, Singh SK, Ferguson DA Jr (2008) The protective function of human C-reactive protein in mouse models of streptococcus pneumoniae infection. Endocr Metab Immune Disord Drug Targets 8(4):231–237

    Article  CAS  PubMed  Google Scholar 

  6. Pankow JS, Folsom AR, Cushman M et al (2001) Familial and genetic determinants of systemic markers of inflammation: The NHLBI family heart study. Atherosclerosis 154(3):681–689

    Article  CAS  PubMed  Google Scholar 

  7. Retterstol L, Eikvar L, Berg K (2003) A twin study of C-reactive protein compared to other risk factors for coronary heart disease. Atherosclerosis 169(2):279–282

    Article  CAS  PubMed  Google Scholar 

  8. MacGregor AJ, Gallimore JR, Spector TD, Pepys MB (2004) Genetic effects on baseline values of C-reactive protein and serum amyloid A protein: A comparison of monozygotic and dizygotic twins. Clin Chem 50(1):130–134

    Article  CAS  PubMed  Google Scholar 

  9. Woo P, Korenberg JR, Whitehead AS (1985) Characterization of genomic and complementary DNA sequence of human C-reactive protein, and comparison with the complementary DNA sequence of serum amyloid P component. J Biol Chem 260(24):13384–13388

    CAS  PubMed  Google Scholar 

  10. Walsh MT, Divane A, Whitehead AS (1996) Fine mapping of the human pentraxin gene region on chromosome 1q23. Immunogenetics 44(1):62–69

    Article  CAS  PubMed  Google Scholar 

  11. Hage FG, Szalai AJ (2007) C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk. J Am Coll Cardiol 50(12):1115–1122

    Article  CAS  PubMed  Google Scholar 

  12. Ridker PM, Pare G, Parker A et al (2008) Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the women's genome health study. Am J Hum Genet 82(5):1185–1192

    Article  CAS  PubMed  Google Scholar 

  13. Morita A, Nakayama T, Soma M (2006) Association study between C-reactive protein genes and ischemic stroke in Japanese subjects. Am J Hypertens 19(6):593–600

    Article  CAS  PubMed  Google Scholar 

  14. Eklund C, Kivimaki M, Islam MS et al (2008) C-reactive protein genetics is associated with carotid artery compliance in men in the cardiovascular risk in young Finns study. Atherosclerosis 196(2):841–848

    Article  CAS  PubMed  Google Scholar 

  15. Zee RY, Germer S, Thomas A et al (2008) C-reactive protein gene variation and type 2 diabetes mellitus: a case-control study. Atherosclerosis 197(2):931–936

    Article  CAS  PubMed  Google Scholar 

  16. Zacho J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG (2008) Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med 359(18):1897–1908

    Article  CAS  PubMed  Google Scholar 

  17. Roy S, Hill AV, Knox K, Griffiths D, Crook D (2002) Research pointers: association of common genetic variant with susceptibility to invasive pneumococcal disease. BMJ 324(7350):1369

    Article  CAS  PubMed  Google Scholar 

  18. Eklund C, Huttunen R, Syrjanen J, Laine J, Vuento R, Hurme M (2006) Polymorphism of the C-reactive protein gene is associated with mortality in bacteraemia. Scand J Infect Dis 38(11–12):1069–1073

    Article  CAS  PubMed  Google Scholar 

  19. Perry TE, Muehlschlegel JD, Liu KY et al (2009) C-reactive protein gene variants are associated with postoperative C-reactive protein levels after coronary artery bypass surgery. BMC Med Genet 10(1):38

    Article  PubMed  Google Scholar 

  20. Conterno LO, Wey SB, Castelo A (1998) Risk factors for mortality in Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol 19(1):32–37

    Article  CAS  PubMed  Google Scholar 

  21. Soriano A, Martinez JA, Mensa J et al (2000) Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia. Clin Infect Dis 30(2):368–373

    Article  CAS  PubMed  Google Scholar 

  22. Benfield T, Espersen F, Frimodt-Moller N et al (2007) Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin Microbiol Infect 13(3):257–263

    Article  CAS  PubMed  Google Scholar 

  23. Mylotte JM, Tayara A (2000) Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort. Clin Infect Dis 31(5):1170–1174

    Article  CAS  PubMed  Google Scholar 

  24. Fowler VG Jr, Olsen MK, Corey GR et al (2003) Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med 163(17):2066–2072

    Article  PubMed  Google Scholar 

  25. Fatkenheuer G, Preuss M, Salzberger B et al (2004) Long-term outcome and quality of care of patients with Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 23(3):157–162

    Article  CAS  PubMed  Google Scholar 

  26. Ruotsalainen E, Jarvinen A, Koivula I et al (2006) Levofloxacin does not decrease mortality in Staphylococcus aureus bacteraemia when added to the standard treatment: a prospective and randomized clinical trial of 381 patients. J Intern Med 259(2):179–190

    Article  CAS  PubMed  Google Scholar 

  27. Jackson GG, Arana-Sialer JA, Andersen BR, Grieble HG, McCabe WR (1962) Profiles of pyelonephritis. Arch Intern Med 110:63–75

    CAS  PubMed  Google Scholar 

  28. Mermel LA, Farr BM, Sherertz RJ et al (2001) Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 32(9):1249–1272

    Article  CAS  PubMed  Google Scholar 

  29. Ruotsalainen E, Sammalkorpi K, Laine J et al (2006) Clinical manifestations and outcome in Staphylococcus aureus endocarditis among injection drug users and nonaddicts: a prospective study of 74 patients. BMC Infect Dis 6:137

    Article  PubMed  Google Scholar 

  30. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B Methodol 57(1):289–300

    Google Scholar 

  31. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265

    Article  CAS  PubMed  Google Scholar 

  32. Szalai AJ, Wu J, Lange EM et al (2005) Single-nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level. J Mol Med 83(6):440–447

    Article  CAS  PubMed  Google Scholar 

  33. Ruotsalainen E, Karden-Lilja M, Kuusela P et al (2008) Methicillin-sensitive Staphylococcus aureus bacteraemia and endocarditis among injection drug users and nonaddicts: host factors, microbiological and serological characteristics. J Infect 56(4):249–256

    Article  PubMed  Google Scholar 

  34. Kovacs A, Green F, Hansson LO et al (2005) A novel common single nucleotide polymorphism in the promoter region of the C-reactive protein gene associated with the plasma concentration of C-reactive protein. Atherosclerosis 178(1):193–198

    Article  CAS  PubMed  Google Scholar 

  35. Kathiresan S, Larson MG, Vasan RS et al (2006) Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein level. Circulation 113(11):1415–23

    Article  CAS  PubMed  Google Scholar 

  36. Suk Danik J, Chasman DI, Cannon CP et al (2006) Influence of genetic variation in the C-reactive protein gene on the inflammatory response during and after acute coronary ischemia. Ann Hum Genet 70(Pt 6):705–16

    Article  CAS  PubMed  Google Scholar 

  37. Ridker PM (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107(3):363–369

    Article  PubMed  Google Scholar 

  38. Wolford JK, Gruber JD, Ossowski VM et al (2003) A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians. Mol Genet Metab 78(2):136

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. Mölkänen.

Additional information

The first two authors contributed equally to this work.

Electronic supplementary materials

Below is the link to the electronic supplementary material.

10096_2010_978_MOESM1_ESM.doc

First week median C-reactive protein levels in Staphylococcus aureus bacteremia and distribution of CRP gene SNPs in 145 patients.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mölkänen, T., Rostila, A., Ruotsalainen, E. et al. Genetic polymorphism of the C-reactive protein (CRP) gene and a deep infection focus determine maximal serum CRP level in Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 29, 1131–1137 (2010). https://doi.org/10.1007/s10096-010-0978-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-010-0978-z

Keywords

Navigation