Riley Thomas R, Wheeler Austin M, Cannon Grant W, Sauer Brian, Wysham Katherine D, England Bryant R, Wipfler Kristin, Michaud Kaleb, March Michael, Damrauer Scott M, Verma Anurag, George Michael D, Mikuls Ted R, Baker Joshua F
University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Rheumatology (Oxford). 2025 Jun 1;64(6):3921-3928. doi: 10.1093/rheumatology/keaf069.
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.
在类风湿关节炎（RA）患者中，我们评估了一个先前与较低C反应蛋白（CRP）相关的单核苷酸变异，以评估其是否会影响临床疾病活动度评估，包括含CRP的28关节疾病活动评分（DAS28(CRP)）。
对来自三个观察性队列的患者进行了评估，即英国生物银行（UKB）、退伍军人事务部RA注册库（VARA）和FORWARD数据库。使用针对性别、年龄和人群结构进行调整的线性回归评估rs1205基因型对经对数调整的血清CRP浓度的影响。将来自UKB的回归系数进行转换，以创建修正的CRP和DAS28(CRP)。确定重新分类为CRP异常（>0.8mg/dl）以及在DAS28(CRP)疾病活动度组之间的情况。
在488377名UKB参与者中，与CC基因型相比，TT和CT基因型个体的经对数调整的CRP在统计学上显著更低[β TT基因型：-0.371（95%CI -0.381，-0.360），P<0.001；β CT基因型：-0.173（95%CI -0.179，-0.167），P<0.001]。在2597名VARA参与者中，与CC基因型相比，TT基因型的DAS28(CRP)显著更低[β -0.22，（95%CI -0.44，-0.0027），P = 0.047]，但CT基因型则不然。在TT基因型个体中，6 - 8%被重新分类为CRP异常，3%的患者从低疾病活动度重新分类为中度疾病活动度。
CRP中的rs1205 TT基因型与较低的CRP和DAS28(CRP)相关。鉴于CRP的广泛应用，这表明遗传因素，无论个体患者的疾病活动度如何，均可导致影响疾病活动度评估的CRP差异。
