Research Article: A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation

Date Published: September 21, 2010

Publisher: Public Library of Science

Author(s): Benjamin Rhodes, Marilyn E. Merriman, Andrew Harrison, Michael J. Nissen, Malcolm Smith, Lisa Stamp, Sophia Steer, Tony R. Merriman, Timothy J. Vyse, Aroon Hingorani

Abstract: A genetic association study by Timothy Vyse and colleagues suggests that there is a significant association between CRP variants and acute-phase serum CRP concentrations in patients with rheumatoid arthritis, including those with chronic inflammation.

Partial Text: Genetic variants at the CRP locus influence the low, basal levels of serum C-reactive protein (CRP) in apparently healthy individuals [1]–[5]. The primary motivation for these existing studies has been the observation of a strong correlation between basal CRP and future cardiovascular risk, and the possibility, now looking less likely, that CRP has a causal role in this process [6],[7]. The widespread clinical application of CRP measurement, however, is not related to its low-level variation within the basal range, but to the high levels seen as part of the human acute-phase response. Serum CRP levels greater than 10 mg/l are generally considered indicative of an infectious or inflammatory process [8]. CRP expression increases rapidly following an inflammatory stimulus, leading to serum levels that may exceed 500 times baseline, making CRP an ideal marker for the diagnosis and monitoring of inflammatory processes. Serum CRP is extensively used in all medical specialities for this purpose [8]. Surprisingly, there has been little published data on the role of CRP variants in determining the magnitude of this acute-phase response, and none in the context of chronic active inflammation.

In patient set 1 the median serum CRP was 11 mg/l (range 1–195; 5th, 95th centiles 5, 88). 51.8% of CRP measurements were >10 mg/l. The median ESR was 22.5 mm/h (range 2–132; 5th, 95th centiles 4, 83). The six genotyped SNPs (with minor allele frequency) were rs2808632 (0.28), rs3093059 (0.07), rs1800947 (0.08), rs1205 (0.35), rs876538 (0.23), and rs11265257 (0.40). In a preliminary analysis, unadjusted for background inflammatory status (ESR), significant associations between serum CRP and SNPs rs1205, rs11265257, and rs1800947 were observed (Tables S1 and S2). In contrast, ESR was not associated with any CRP SNP (Table S3).



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