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Observational Study
. 2025 Jun 1;64(6):3921-3928.
doi: 10.1093/rheumatology/keaf069.

Genetically-determined variation in CRP impacts disease activity assessment in rheumatoid arthritis

Thomas R Riley  1   2 , Austin M Wheeler  3   4 , Grant W Cannon  5 , Brian Sauer  5 , Katherine D Wysham  6 , Bryant R England  3   4 , Kristin Wipfler  7 , Kaleb Michaud  4   7 , Michael March  8 , Scott M Damrauer  1   2 , Anurag Verma  1   2 , Michael D George  1 , Ted R Mikuls  3   4 , Joshua F Baker  1   2
Affiliations
Observational Study

Genetically-determined variation in CRP impacts disease activity assessment in rheumatoid arthritis

Thomas R Riley et al. Rheumatology (Oxford). .

Abstract

Objectives: In patients with RA, we evaluated a single-nucleotide variant previously associated with lower CRP to assess if this impacts clinical disease activity assessments including the disease activity score-28 with CRP (DAS28(CRP)).

Methods: Patients from three observational cohorts were evaluated-the United Kingdom Biobank (UKB), the Veterans Affairs RA Registry (VARA) and the FORWARD Databank. The effect of rs1205 genotype on log-adjusted serum CRP concentrations was assessed using linear regression adjusted for sex, age and population structure. The regression coefficients from UKB were converted to create a modified CRP and DAS28(CRP). Reclassification to an abnormal CRP (>0.8 mg/dl) and between DAS28(CRP) disease activity groups were determined.

Results: Among the 488 377 UKB participants, individuals with the TT and CT genotype had a statistically significantly lower log-adjusted CRP compared with the CC genotype [β TT genotype: -0.371 (95% CI -0.381, -0.360), P < 0.001; β CT genotype: -0.173 (95% CI -0.179, -0.167), P < 0.001]. In the 2597 VARA participants, the DAS28(CRP) was significantly lower in the genotype TT compared with the CC genotype [β -0.22, (95% CI -0.44, -0.0027), P = 0.047], but not in the CT genotype. In those with the TT genotype, 6-8% were reclassified to having an abnormal CRP and 3% of patients were reclassified from low to moderate disease activity.

Conclusion: The rs1205 TT genotype in CRP is associated with lower CRP and DAS28(CRP). Given the widespread use of CRP, this demonstrates that genetic factors, irrespective of an individual patient's disease activity, can cause differences in CRP that impact disease activity assessment.

Keywords: CRP; RA; candidate gene study; disease activity assessment.

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Figures

Figure 1.
Figure 1.
(A) Unadjusted and correction factor-modified mean CRP (mg/dl) by CRP rs1205 genotype. (B) Unadjusted and correction factor-modified mean DAS28(CRP) by CRP rs1205 genotype
Figure 2.
Figure 2.
(A) Observed and (B) correction factor-modified plots of log-transformed ESR (mm/h) vs log-transformed CRP (mg/dl), by CRP rs1205 genotype, with fractional polynomial curve fitting. Gray shading represents 95% confidence intervals
See this image and copyright information in PMC

References

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