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THU0007 Investigation of CRP Gene Polymorphisms as Predictors of Cardiovascular Mortality in Inflammatory Polyarthritis – Results from the Norfolk Arthritis Register
  1. I. Ibrahim1,
  2. D. Plant1,2,
  3. M. Lunt1,
  4. S. Verstappen1,
  5. E. Flynn1,
  6. D. Symmons1,2,
  7. A. Barton1,2
  1. 1Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, University of Manchester
  2. 2NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom

Abstract

Background Patients with rheumatoid arthritis (RA) and inflammatory polyarthritis (IP) are at increased risk of premature death compared to the general population, with cardiovascular disease (CVD) forming the primary cause. C-reactive protein (CRP), an acute-phase inflammatory marker, is elevated in RA patients and previous investigations have shown that those patients with the most active disease are at greatest risk of CVD mortality. However, functional variants exist within the CRP gene that affect basal CRP production, and could, therefore, influence the risk of CVD in RA.

Objectives To determine the relationship between functional genetic variants at the CRP gene locus (rs1205, rs1800947 & rs3091244) and levels of serum CRP in IP patients, and to determine whether these variants are correlated with all-cause and CVD mortality in IP.

Methods Patients in this study were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based prospective inception cohort of patients with new onset IP.

DNA samples from NOAR were genotyped for 3 single nucleotide polymorphism (SNP) markers (rs1205, rs1800947 & rs3091244) using either TaqMan® or the Sequenom® MassARRAY iPLEX system. Estimated haplotypes were constructed in the haplo.stats package within the R statistical environment. Death certificates of all patients in NOAR were obtained from the Office for National Statistics (ONS). In the current study, all-cause mortality or CVD mortality (ICD10-code “I”) were used as the outcome. All patients were followed from disease symptom onset until death, embarkation, or June 30, 2010, whichever came first. The association between SNPs (and haplotypes of SNPs), and baseline CRP levels was evaluated using zero-inflated negative binomial regression. Cox proportional hazard models were used to investigate the association between CRP SNP marker allele carriage and CRP haplotypes, with risk of all-cause mortality, and CVD mortality, adjusting for known CVD risk factors, e.g. age, gender, smoking status, cholesterol, hypertension, diabetes and obesity.

Results DNA and baseline serum CRP measurements were available for 1,745 samples. Median symptom duration prior to presentation was 7 months (IQR 3-14), and 1,347 patients were female (66%). During follow-up, 921 patients (45%) satisfied the ACR 1987 criteria for RA. By June 30, 2010, 450 patients (22%) had died, and CVD was recorded on the death certificate for 261 patients (58% of all deaths). CRP SNPs were associated with baseline levels of CRP in patients who carried a single copy of rs1205 (p=0.003), a single copy of rs1800947 (p=0.01), and two copies of the T allele of rs3091244 (0.04). No association was observed between any of the CRP haplotypes investigated and baseline CRP (p=0.10). Further, CRP markers and haplotypes did not correlate with all-cause mortality (p=0.26 and 0.77, respectively), or CVD mortality (p=0.53 and 0.79, respectively), even after adjusting for known CVD risk factors.

Conclusions CRP genotype does not influence either all-cause or CVD mortality in a large cohort of IP patients. Therefore, inflammation as assessed by CRP measurements, although previously shown to predict CVD in IP, is not directly responsible for the development of CVD in such patients.

Disclosure of Interest None Declared

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