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CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients.

ABSTRACT: 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.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.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).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.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.

SUBMITTER: Ammitzboll CG

PROVIDER: S-EPMC4247621 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients.

Ammitzbøll Christian Gytz CG Steffensen Rudi R Bøgsted Martin M Hørslev-Petersen Kim K Hetland Merete L ML Junker Peter P Johansen Julia S JS Pødenphant Jan J Østergaard Mikkel M Ellingsen Torkell T Stengaard-Pedersen Kristian K

Arthritis research & therapy 20141031 5

<h4>Introduction</h4>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, a ...[more]

PMID: 25359432

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Project description:Rheumatoid arthritis (RA) is influenced by oral and gut bacteria; however, much less is known about the relationship between oral or gut viromes and RA. Here, we performed whole-oral- and whole-gut-virome analyses based on shotgun sequencing of 497 samples. A comparative analysis of the oral and gut viromes in healthy controls and untreated and treated RA patients was performed, and system interaction networks among viruses, bacteria, and RA-associated clinical indices were constructed to address the potential relationship between the virome and RA by principal-coordinate analysis, distance-based redundancy analysis, permutational multivariate analysis, Spearman correlation coefficient analysis, and random-forest model analysis. The results showed that the viromes could be profiled in dental plaque, saliva, and fecal samples, among which saliva had the highest within-sample diversity. Importantly, significantly different diversities and compositions of the oral (i.e., dental plaque and saliva) viromes were observed not only between RA patients and healthy controls but also between untreated and treated RA patients, yet there were relatively minor differences in the gut viromes. Furthermore, to understand how these viruses affected the bacteriome, a virus-bacterium interaction network was constructed from dental plaque, saliva, and fecal samples of RA patients. Additionally, some RA-associated oral taxa, including Lactococcus phage (vOTU70), Bacteroides vulgatus, Lactococcus lactis, Escherichia coli, and Neisseria elongata, were correlated with the RA-related clinical indices. Whole-virome analysis illustrated the potential role of the oral and gut viromes in affecting our body either directly or via bacteria, which characterized neglected and new candidates contributing to the development of RA. IMPORTANCE Our results demonstrated community variation among dental plaque, saliva, and fecal viromes. In oral and gut samples from untreated and treated RA patients, the perturbance of viral composition and the correlation network of microbes and RA-associated clinical indices might be involved in the pathogenicity of RA. The findings in this study expand the knowledge of the potential role of oral and gut viral communities in the development of RA and may contribute to research on correlations between viruses and other diseases.

Dataset Information

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients.

Publications

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients.

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