A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation
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{"title"=>"A genetic association study of serum acute-phase C-reactive protein levels in rheumatoid arthritis: Implications for clinical interpretation", "type"=>"journal", "authors"=>[{"first_name"=>"Benjamin", "last_name"=>"Rhodes", "scopus_author_id"=>"24076981400"}, {"first_name"=>"Marilyn E.", "last_name"=>"Merriman", "scopus_author_id"=>"7004267248"}, {"first_name"=>"Andrew", "last_name"=>"Harrison", "scopus_author_id"=>"7401690588"}, {"first_name"=>"Michael J.", "last_name"=>"Nissen", "scopus_author_id"=>"8930465400"}, {"first_name"=>"Malcolm", "last_name"=>"Smith", "scopus_author_id"=>"14029036900"}, {"first_name"=>"Lisa", "last_name"=>"Stamp", "scopus_author_id"=>"6602140085"}, {"first_name"=>"Sophia", "last_name"=>"Steer", "scopus_author_id"=>"6603951069"}, {"first_name"=>"Tony R.", "last_name"=>"Merriman", "scopus_author_id"=>"7003535346"}, {"first_name"=>"Timothy J.", "last_name"=>"Vyse", "scopus_author_id"=>"7003955999"}], "year"=>2010, "source"=>"PLoS Medicine", "identifiers"=>{"pui"=>"359754405", "sgr"=>"77957872865", "issn"=>"15491277", "pmid"=>"20877716", "scopus"=>"2-s2.0-77957872865", "doi"=>"10.1371/journal.pmed.1000341", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)"}, "id"=>"935d13a5-95f8-37cc-807d-19b29ca80e64", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/genetic-association-study-serum-acutephase-creactive-protein-levels-rheumatoid-arthritis-implication", "reader_count"=>17, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>5, "Agricultural and Biological Sciences"=>7, "Psychology"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/828952"], "description"=>"<p>Single <i>CRP</i> SNP effects on acute-phase serum CRP.</p>", "links"=>[], "tags"=>["snp", "acute-phase", "serum"], "article_id"=>499313, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Benjamin Rhodes", "Marilyn E. Merriman", "Andrew Harrison", "Michael J. Nissen", "Malcolm Smith", "Lisa Stamp", "Sophia Steer", "Tony R. Merriman", "Timothy J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1000341.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_CRP_SNP_effects_on_acute_phase_serum_CRP_/499313", "title"=>"Single <i>CRP</i> SNP effects on acute-phase serum CRP.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-21 02:35:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/412784", "https://ndownloader.figshare.com/files/412788", "https://ndownloader.figshare.com/files/412791", "https://ndownloader.figshare.com/files/412796", "https://ndownloader.figshare.com/files/412799", "https://ndownloader.figshare.com/files/412807"], "description"=>"<div><h3>Background</h3><p>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.</p><h3>Methods and Findings</h3><p>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 <em>CRP</em> 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 <em>CRP</em> locus were associated with acute-phase serum CRP (for the most associated haplotype: <em>p</em> = 0.002, <em>p<</em>0.0005, <em>p<</em>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 <em>CRP</em> 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.</p><h3>Conclusions</h3><p>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 <em>CRP</em> genotype alone. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement.</p><h3></h3><p><em>Please see later in the article for the Editors' Summary</em></p></div>", "links"=>[], "tags"=>["serum", "acute-phase", "c-reactive", "levels", "rheumatoid", "implications"], "article_id"=>141541, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Benjamin Rhodes", "Marilyn E. Merriman", "Andrew Harrison", "Michael J. Nissen", "Malcolm Smith", "Lisa Stamp", "Sophia Steer", "Tony R. Merriman", "Timothy J. Vyse"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1000341.s001", "https://dx.doi.org/10.1371/journal.pmed.1000341.s002", "https://dx.doi.org/10.1371/journal.pmed.1000341.s003", "https://dx.doi.org/10.1371/journal.pmed.1000341.s004", "https://dx.doi.org/10.1371/journal.pmed.1000341.s005", "https://dx.doi.org/10.1371/journal.pmed.1000341.s006"], "stats"=>{"downloads"=>33, "page_views"=>40, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Genetic_Association_Study_of_Serum_Acute_Phase_C_Reactive_Protein_Levels_in_Rheumatoid_Arthritis_Implications_for_Clinical_Interpretation/141541", "title"=>"A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-09-21 00:25:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/828910"], "description"=>"<p>CRP parameter estimates (geometric mean) from the combined cohorts.</p>", "links"=>[], "tags"=>["parameter", "estimates"], "article_id"=>499270, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Benjamin Rhodes", "Marilyn E. Merriman", "Andrew Harrison", "Michael J. Nissen", "Malcolm Smith", "Lisa Stamp", "Sophia Steer", "Tony R. Merriman", "Timothy J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1000341.t002", "stats"=>{"downloads"=>3, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CRP_parameter_estimates_geometric_mean_from_the_combined_cohorts_/499270", "title"=>"CRP parameter estimates (geometric mean) from the combined cohorts.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-21 02:34:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/828872"], "description"=>"<p><i>CRP</i> haplotype architecture and frequency.</p>", "links"=>[], "tags"=>["haplotype"], "article_id"=>499240, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Benjamin Rhodes", "Marilyn E. Merriman", "Andrew Harrison", "Michael J. Nissen", "Malcolm Smith", "Lisa Stamp", "Sophia Steer", "Tony R. Merriman", "Timothy J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1000341.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CRP_haplotype_architecture_and_frequency_/499240", "title"=>"<i>CRP</i> haplotype architecture and frequency.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-21 02:34:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/828762"], "description"=>"<p>Annotated by the haplotype pair (A), or grouping (B), represented on the graph, with the population frequency of that combination. Data from the combined cohorts.</p>", "links"=>[], "tags"=>["acute-phase", "crp", "stratified", "esr-defined"], "article_id"=>499115, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Benjamin Rhodes", "Marilyn E. Merriman", "Andrew Harrison", "Michael J. Nissen", "Malcolm Smith", "Lisa Stamp", "Sophia Steer", "Tony R. Merriman", "Timothy J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1000341.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_acute_phase_CRP_level_95_CI_stratified_by_haplotype_and_according_to_the_ESR_defined_level_of_background_inflammation_/499115", "title"=>"Predicted acute-phase CRP level (95% CI), stratified by haplotype, and according to the ESR-defined level of background inflammation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-21 02:31:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/828825"], "description"=>"<p><i>CRP</i> haplotype effect on acute-phase serum CRP.</p>", "links"=>[], "tags"=>["haplotype", "acute-phase", "serum"], "article_id"=>499182, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Benjamin Rhodes", "Marilyn E. Merriman", "Andrew Harrison", "Michael J. Nissen", "Malcolm Smith", "Lisa Stamp", "Sophia Steer", "Tony R. Merriman", "Timothy J. Vyse"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1000341.t004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CRP_haplotype_effect_on_acute_phase_serum_CRP_/499182", "title"=>"<i>CRP</i> haplotype effect on acute-phase serum CRP.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-21 02:33:02"}

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Relative Metric

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