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SAT0282 C-reactive protein (CRP) polymorphisms and haplotypes influence serum CRP levels independent of disease activity (BASDAI) in ankylosing spondylitis
  1. T.A. Claushuis1,
  2. M.K. de Vries1,
  3. I.E. van der Horst-Bruinsma1,
  4. M.A. van der Weijden1,
  5. I.M. Visman2,
  6. M.T. Nurmohamed2,
  7. J.W. Twisk3,
  8. J.B. Crusius4
  1. 1Department of Rheumatology, VU University Medical Center
  2. 2Jan van Breemen Research Institute/Reade
  3. 3Department of Methodology and Applied Biostatistics, VU University
  4. 4Laboratory for Immunogenetics at the Department of Pathology, VU University Medical Center, Amsterdam, Netherlands

Abstract

Background C-reactive protein (CRP) levels are used more frequently for determination of disease activity in patients with Ankylosing Spondylitis (AS), but these levels do not necessarily reflect disease activity in each patient.

Objectives We investigated whether CRP levels were influenced by common single-nucleotide polymorphisms (SNPs) and haplotypes in the CRP gene in AS patients. Additionally, we studied the relation between CRP levels and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

Methods In this exploratory cross-sectional study, 189 unrelated anti-tumour necrosis factor naïve Dutch Caucasian AS patients were included and CRP SNPs rs2794521, rs3091244, rs1800947, and rs876538 were genotyped and haplotypes constructed. We used a multivariate linear and logistic regression model to investigate the relation between the SNPs and baseline CRP levels (mg/l), controlling for NSAID use, BMI, smoking, age, sex, and using the BASDAI to correct for disease activity.

Results CRP levels were significantly positively correlated with the BASDAI (p=0.001). AS patients with genotype CA of the tri-allelic (C>T>A) SNP rs3091244 were associated with significantly higher CRP levels when compared with genotype CC (CA: 18.6 mg/l vs. CC: 8.3 mg/l; p=0.02). Heterozygous carriers of haplotype 5 (tagged by allele A of rs3091244) had a significantly higher odd when compared with non-carriers to have a CRP value >10 mg/l (OR=2.9, 95%CI 1.0 to 8.3; p=0.05) in the multivariate regression model.

Figure 1. Baseline CRP values in mg/l for the SNP rs3091244 observed genotypes. CRP values were backtransformed after natural logarithmic correction. Data are represented as mean ± upper 95% CI. P values are indicated.

Conclusions Certain CRP polymorphisms (SNP rs3091244 genotypes) and the haplotype tagged by allele A are associated with high CRP levels in AS, independent of the BASDAI and other confounders. Therefore, carrying distinct genetic variants might explain the lack of elevated CRP levels despite high disease activity in certain AS patients. This observation can be important to interpret disease activity scores that incorporate CRP levels, like the Ankylosing Spondylitis Disease Activity Score (ASDAS).

Disclosure of Interest None Declared

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