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

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.

Neonatal infections in Saudi Arabia: association with C-reactive protein, CRP -286 (C>T>A) gene polymorphism and IgG antibodies

“…Our data is in agreement with a recent study which focused on deep infections, where CRP-286 (C>T>A) polymorphism is found to be significantly associated with maximal CRP levels during the first week of infection [46]. Interestingly, this same triallelic CRP-286 (C>T>A) polymorphism, which we found to be associated with maximal CRP levels in S. aureus bacteraemia, has been related to high basal CRP levels as well [14,46-49]. The triallelic SNP association with CRP level strongly supports recent work described above and represents a reproducible association between genetic variation and this biomarker of high interest.…”

“…This result mirrors a previous study which found a similar relationship between higher frequencies of A-allele carriers and higher concentration of serum CRP levels [14]. Our data is in agreement with a recent study which focused on deep infections, where CRP-286 (C>T>A) polymorphism is found to be significantly associated with maximal CRP levels during the first week of infection [46]. Interestingly, this same triallelic CRP-286 (C>T>A) polymorphism, which we found to be associated with maximal CRP levels in S. aureus bacteraemia, has been related to high basal CRP levels as well [14,46-49].…”

Predictive Value of C-Reactive Protein (CRP) in Identifying Fatal Outcome and Deep Infections in Staphylococcus aureus Bacteremia

“…CRP has been recognized as a good marker of systemic inflammation and a valuable clinical tool in severe infections [ 18 ], but clear cut-off levels to guide clinical decisions in SAB have not been demonstrated. The maximal CRP level might not be useful because it is influenced by genetic variation in the genes responsible for CRP synthesis [ 19 ]. This study was undertaken to assess CRP concentrations at various time points during SAB infection that would enable to identify patients with complications.…”

Modeling C-Reactive Protein Kinetic Profiles for Use as a Clinical Prediction Tool in Patients With Staphylococcus Aureus Bacteremia

“…Potentially important clinical characteristics particularly the details of antibiotic therapy, the role and timing of surgery, sepsis severity and presence of in hospital complications were not well captured in the database or incorporated into the model. The impacts of liver disease and CRP polymorphisms [22][23][24][25][26] were beyond the scope of the study and could not be accounted for in the model. Such limitations impact both the performance of the model at a population level (particularly over longer time periods) and its ability to control for significant covariates when defining the relationship between CRP and key outcomes.…”