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

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)).

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.

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.

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.