TY - JOUR
T1 - CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients
AU - Ammitzbøll, Christian
AU - Steffensen, Rudi
AU - Bøgsted, Martin
AU - Hørslev-Petersen, Kim
AU - Hetland, Merete L
AU - Junker, Peter
AU - Johansen, Julia S
AU - Pødenphanth, Jan
AU - Østergaard, Mikkel
AU - Ellingsen, Torkell
AU - Stengaard-Pedersen, Kristian
PY - 2014/10/31
Y1 - 2014/10/31
N2 - IntroductionSingle nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to pro-inflammatory stimuli. Previous reports suggest these effects may have an impact on clinical decision-making based on CRP, for example DAS28. We aimed to investigate the possible association between 7 CRP SNPs, their haplotypes, and the serum level of CRP as well as the DAS28 score in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment.MethodsOverall, 315 disease-modifying anti-rheumatic drugs and steroid naïve RA patients with disease duration <6 months were included from two randomized controlled trials (the CIMESTRA and OPERA trials). Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations to CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment.ResultsThe 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 one (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 one (P =0.466). No other SNP or haplotype was associated with CRP at baseline or year one (P ¿0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or year one (P ¿0.10).Conclusion CRP genotype and haplotype were only marginally associated with serum CRP levels and without any association to 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.Trial registrationThe OPERA study is registered at clinicaltrials.gov (NCT00660647). The Cimestra study is not listed in a clinical trials registry due to inclusion of patients between October 1999 and October 2002.
AB - IntroductionSingle nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to pro-inflammatory stimuli. Previous reports suggest these effects may have an impact on clinical decision-making based on CRP, for example DAS28. We aimed to investigate the possible association between 7 CRP SNPs, their haplotypes, and the serum level of CRP as well as the DAS28 score in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment.MethodsOverall, 315 disease-modifying anti-rheumatic drugs and steroid naïve RA patients with disease duration <6 months were included from two randomized controlled trials (the CIMESTRA and OPERA trials). Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations to CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment.ResultsThe 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 one (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 one (P =0.466). No other SNP or haplotype was associated with CRP at baseline or year one (P ¿0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or year one (P ¿0.10).Conclusion CRP genotype and haplotype were only marginally associated with serum CRP levels and without any association to 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.Trial registrationThe OPERA study is registered at clinicaltrials.gov (NCT00660647). The Cimestra study is not listed in a clinical trials registry due to inclusion of patients between October 1999 and October 2002.
U2 - 10.1186/s13075-014-0475-3
DO - 10.1186/s13075-014-0475-3
M3 - Journal article
C2 - 25359432
SN - 1478-6354
VL - 16
SP - 475
JO - Arthritis Research & Therapy
JF - Arthritis Research & Therapy
IS - 5
ER -