Document Detail


A genetic association study of serum acute-phase C-reactive protein levels in rheumatoid arthritis: implications for clinical interpretation.
MedLine Citation:
PMID:  20877716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The acute-phase increase in serum C-reactive protein (CRP) is used to diagnose and monitor infectious and inflammatory diseases. Little is known about the influence of genetics on acute-phase CRP, particularly in patients with chronic inflammation.
METHODS AND FINDINGS: We studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients). A tagSNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. Erythrocyte sedimentation rate (ESR) was incorporated as an independent marker of inflammation to adjust for the varying levels of inflammatory disease activity between patients. Common genetic variants at the CRP locus were associated with acute-phase serum CRP (for the most associated haplotype: p = 0.002, p<0.0005, p<0.0005 in patient sets 1, 2, and the combined sets, respectively), translating into an approximately 3.5-fold change in expected serum CRP concentrations between carriers of two common CRP haplotypes. For example, when ESR = 50 mm/h the expected geometric mean CRP (95% confidence interval) concentration was 43.1 mg/l (32.1-50.0) for haplotype 1 and 14.2 mg/l (9.5-23.2) for haplotype 4.
CONCLUSIONS: Our findings raise questions about the interpretation of acute-phase serum CRP. In particular, failure to take into account the potential for genetic effects may result in the inappropriate reassurance or suboptimal treatment of patients simply because they carry low-CRP-associated genetic variants. CRP is increasingly being incorporated into clinical algorithms to compare disease activity between patients and to predict future clinical events: our findings impact on the use of these algorithms. For example, where access to effective, but expensive, biological therapies in rheumatoid arthritis is rationed on the basis of a DAS28-CRP clinical activity score, then two patients with identical underlying disease severity could be given, or denied, treatment on the basis of CRP genotype alone. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement.
Authors:
Benjamin Rhodes; Marilyn E Merriman; Andrew Harrison; Michael J Nissen; Malcolm Smith; Lisa Stamp; Sophia Steer; Tony R Merriman; Timothy J Vyse
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-21
Journal Detail:
Title:  PLoS medicine     Volume:  7     ISSN:  1549-1676     ISO Abbreviation:  PLoS Med.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-29     Completed Date:  2011-01-18     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101231360     Medline TA:  PLoS Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1000341     Citation Subset:  IM    
Affiliation:
Rheumatology Section, Division of Medicine, Imperial College London, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Arthritis, Rheumatoid / blood,  diagnosis,  genetics*
Blood Sedimentation
C-Reactive Protein / genetics*,  metabolism*
Genetic Association Studies
Genotype
Haplotypes
Humans
Polymorphism, Single Nucleotide
Grant Support
ID/Acronym/Agency:
18544//Arthritis Research UK
Chemical
Reg. No./Substance:
9007-41-4/C-Reactive Protein
Comments/Corrections
Comment In:
Nat Rev Rheumatol. 2010 Dec;6(12):676   [PMID:  21166084 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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