title: CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  The OPERA study is registered at Clinicaltrials.gov (NCT00660647). The CIMESTRA study is not listed in a clinical trials registry, because patients were included between October 1999 and October 2002.
authors.forename: Christian Gytz
authors.initials: CG
authors.lastname: Ammitzbøll
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.forename: Martin
authors.initials: M
authors.lastname: Bøgsted
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.forename: Merete L
authors.initials: ML
authors.lastname: Hetland
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.forename: Jan
authors.initials: J
authors.lastname: Pødenphant
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.forename: Torkell
authors.initials: T
authors.lastname: Ellingsen
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D002097:C-Reactive Protein