A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis Implications for Clinical Interpretation 英文参考文献.docVIP
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A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis Implications for Clinical Interpretation 英文参考文献
AGeneticAssociationStudyofSerumAcute-Phase
C-ReactiveProteinLevelsinRheumatoidArthritis:
ImplicationsforClinicalInterpretation
BenjaminRhodes1,MarilynE.Merriman2,AndrewHarrison3,MichaelJ.Nissen4,MalcolmSmith4 ,Lisa
Stamp5,SophiaSteer6,TonyR.Merriman2,TimothyJ.Vyse1*
1RheumatologySection,Division ofMedicine,ImperialCollege London, London,United Kingdom, 2Department ofBiochemistry, University ofOtago,Dunedin, New
Zealand,3DepartmentofMedicine,WellingtonSchoolofMedicineandHealthSciences,UniversityofOtago,Dunedin,NewZealand,4RheumatologyUnit,Repatriation
General Hospital, Daw Park, Adelaide, South Australia, Australia, 5Department of Medicine, University of Otago, Christchurch, New Zealand, 6Clinical and Academic
Rheumatology,KingsCollegeHospitalNHSFoundationTrust,London,UnitedKingdom
Abstract
Background:Theacute-phaseincreaseinserumC-reactiveprotein(CRP)isusedtodiagnoseandmonitorinfectiousand
inflammatory diseases. Little is known about the influence of genetics on acute-phase CRP, particularly in patients with
chronicinflammation.
MethodsandFindings:Westudiedtwoindependentsetsofpatientswithchronicinflammationduetorheumatoidarthritis
(total 695 patients). A tagSNP approach captured common variation at the CRP locus and the relationship between
genotypeandserumCRPwasexploredbylinearmodelling.Erythrocytesedimentationrate(ESR)wasincorporatedasan
independent marker of inflammation to adjust for the varying levels of inflammatory disease activity between patients.
CommongeneticvariantsattheCRPlocuswereassociatedwithacute-phaseserumCRP(forthemostassociatedhaplotype:
p=0.002,p,0.0005,p,0.0005inpatientsets1,2,andthecombinedsets,respectively),translatingintoanapproximately
3.5-fold change in expected serum CRP concentrations between carriers of two common CRP haplotypes. For example,
whenESR=50mm/htheexpectedgeometricmeanCRP(95%confidenceinterval)concentrationwas43.1mg/l(32.1–50.0)
forhaplotype1and14.2mg/l(9.5–23.2)forhaplotype4.
Conclusions:Ourfindingsraisequestionsaboutth
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