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, 16 (5), 475

CRP Genotype and Haplotype Associations With Serum C-reactive Protein Level and DAS28 in Untreated Early Rheumatoid Arthritis Patients

CRP Genotype and Haplotype Associations With Serum C-reactive Protein Level and DAS28 in Untreated Early Rheumatoid Arthritis Patients

Christian Gytz Ammitzbøll et al. Arthritis Res Ther.


Introduction: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Score in 28 joints (DAS28). We aimed to investigate the possible association between seven CRP SNPs, their haplotypes and the serum levels of CRP, as well as DAS28 scores, in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment.

Methods: Overall, 315 patients with RA from two randomized controlled trials (the CIMESTRA and OPERA trials) who were naïve to disease-modifying antirheumatic drugs and steroids with disease durations less than 6 months were included. Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment.

Results: The minor allele of rs1205 C > T was associated with decreased CRP levels at baseline (P = 0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P = 0.005) compared to homozygosity of the major allele, but no association was observed at year 1 (P = 0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P = 0.043), although no effect was observed at year 1 (P = 0.466). No other SNP or haplotype was associated with CRP at baseline or at year 1 (P ≥ 0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or at year 1 (P ≥ 0.10).

Conclusion: CRP genotype and haplotype were only marginally associated with serum CRP levels and had no association with the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.

Trial registration: The OPERA study is registered at (NCT00660647). The CIMESTRA study is not listed in a clinical trials registry, because patients were included between October 1999 and October 2002.


Figure 1
Figure 1
Single-nucleotide polymorphisms and haplotypes in the CRP gene. (A) Schematic representation of the CRP gene drawn to scale. Exons are represented as blue boxes. Dots represent the locations of the seven single-nucleotide polymorphisms investigated in this study. Zigzag lines indicate truncation of nucleotides. (B) Haplotypes and names are in agreement with those used in previous publications [16,17]. The nucleotides are stated according to the plus strand. The frequencies of haplotypes are given as percentages.
Figure 2
Figure 2
Serum C-reactive protein concentrations divided by rs1205 genotype at baseline. Serum C-reactive protein (CRP) concentrations of 313 patients with early rheumatoid arthritis at their time of diagnosis according to rs1205 genotype. Circles indicate individual serum CRP concentrations. The boxes indicate geometric means and 95% CIs calculated from linear regression analysis corrected for age, sex and treatment. *P <0.05.

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    1. Bottazzi B, Doni A, Garlanda C, Mantovani A. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol. 2010;28:157–183. doi: 10.1146/annurev-immunol-030409-101305. - DOI - PubMed
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