title: C-reactive protein polymorphisms influence serum CRP-levels independent of disease activity in ankylosing spondylitis.
abstract: OBJECTIVE
  C-reactive protein (CRP) levels are frequently used to determine disease activity in patients with ankylosing spondylitis (AS), but these levels may not reflect disease activity. We therefore investigated the influence of common single-nucleotide polymorphisms (SNPs) in the CRP gene on CRP levels in AS patients. Additionally, the relation between CRP levels and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) was examined.
  
  
  METHODS
  This exploratory cross-sectional study included 189 Dutch AS patients. CRP SNPs rs2794521, rs3091244, rs1800947 and rs876538 were genotyped and haplotypes constructed. Linear regression analysis was used for the association between SNPs and CRP levels, with correction for confounders non-steroidal anti-inflammatory drugs use, body mass index, smoking, age, gender and disease activity (BASDAI).
  
  
  RESULTS
  Only 52% of AS patients with a high disease activity (BASDAI ≥4) showed a high CRP level (≥10mg/L), whereas the others did not. In AS patients, CRP levels changed with different genotypes, with genotype CA of tri-allelic (C>T>A) SNP rs3091244 showing higher CRP levels in comparison with genotype CC (CA: 18.6 mg/L vs. CC: 8.3 mg/L; p=0.02). Carriers of haplotype 5 (tagged by allele A of rs3091244) had a higher risk to express a CRP ≥10 mg/L (OR=2.9, 95%CI 1.0-8.3; p=0.05) when compared with non-carriers.
  
  
  CONCLUSIONS
  In AS, patients with high disease activity often do not show corresponding high CRP levels. We found that CRP levels vary with different CRP genotype in AS patients. Carrying distinct genetic variants might play a role in certain AS patients who show low CRP levels despite high disease activity (as well as high CRP levels with low disease activity). This observation may be important for the interpretation of disease activity scores that incorporate CRP levels, like the ASDAS.
authors.affiliation: Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Theodora A M
authors.initials: TA
authors.lastname: Claushuis
authors.affiliation: Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Mirjam K
authors.initials: MK
authors.lastname: de Vries
authors.affiliation: Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Mignon A C
authors.initials: MA
authors.lastname: van der Weijden
authors.affiliation: Jan van Breemen Research Institute-Reade, Amsterdam, The Netherlands.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Visman
authors.affiliation: Jan van Breemen Research Institute-Reade, Amsterdam, The Netherlands.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Nurmohamed
authors.affiliation: Department of Methodology and Applied Biostatistics, VU University, Amsterdam, The Netherlands.
authors.forename: Jos W R
authors.initials: JW
authors.lastname: Twisk
authors.affiliation: Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Van der Horst-Bruinsma
authors.affiliation: Laboratory for Immunogenetics at the Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jakob B A
authors.initials: JB
authors.lastname: Crusius
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors* / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein