Genetic Variation Affects C-Reactive Protein Elevations in Crohn's Disease

Background: C-reactive protein (CRP) is a serum marker that is used to measure disease activity in Crohn's disease (CD). However, a subset of CD patients have normal CRP during flares. In rheumatoid arthritis and lupus, genetic variants can restrict CRP elevations during flares. This study sought to determine if common CRP genetic variants affect CRP values during active CD.

Methods: Subjects with CD who participated in the Partners HealthCare BioBank were genotyped for 5 common CRP genetic variants (rs2794520, rs3122012, rs3093077, rs2808635, and rs1800947). Medical records were reviewed to determine disease activity and the highest CRP value during active CD. CRP values during active infection or malignancy at the time of the test were excluded. CRP values were compared by genotype using the Mann-Whitney test.

Results: The study included 199 subjects with active CD (21 to 86 years of age). Subjects with the rs2794520 TT genotype had a lower CRP than subjects with the CC genotype (58.3 mg/L vs 28.4 mg/L, P = 0.008). Subjects with the rs1800947 CG genotype had a lower CRP than those with the CC genotype (54.3 mg/L vs 22.4 mg/L, P < 0.0001); 41.6% of TT subjects had a normal CRP compared with 24.1% of CT subjects and 16.5% of CC subjects (P = 0.041).

Conclusions: This study demonstrates that rs2794520 and rs1800947 are associated with a restriction of CRP elevations during active CD. While CRP is typically a reliable biomarker in CD, there is a subset of CD patients with a genetically determined restriction of CRP in whom other disease markers should be utilized.