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

Area of Science:

• Genetics
• Immunology
• Gastroenterology

Background:

• C-reactive protein (CRP) is a key serum marker for assessing disease activity in Crohn's disease (CD).
• A subset of CD patients exhibit normal CRP levels even during active disease flares.
• Genetic variations are known to influence CRP levels during inflammatory conditions like rheumatoid arthritis and lupus.

Purpose of the Study:

• To investigate whether common genetic variants of CRP influence CRP levels during active Crohn's disease flares.
• To identify specific CRP genetic variants associated with restricted CRP elevations in CD patients.

Main Methods:

• Genotyping of 199 Crohn's disease patients for five common CRP genetic variants (rs2794520, rs3122012, rs3093077, rs2808635, rs1800947).
• Review of medical records to determine disease activity and peak CRP values during active CD.
• Exclusion of CRP values from periods of active infection or malignancy; comparison of CRP values by genotype using the Mann-Whitney test.

Main Results:

• The rs2794520 TT genotype was associated with significantly lower CRP levels compared to the CC genotype (28.4 mg/L vs 58.3 mg/L, P = 0.008).
• The rs1800947 CG genotype showed lower CRP levels than the CC genotype (54.3 mg/L vs 22.4 mg/L, P < 0.0001).
• A higher percentage of subjects with the rs2794520 TT genotype (41.6%) had normal CRP levels during active CD compared to CT (24.1%) and CC (16.5%) genotypes (P = 0.041).

Conclusions:

• Specific CRP genetic variants, namely rs2794520 and rs1800947, are linked to a blunted CRP response during active Crohn's disease.
• While CRP is generally a reliable biomarker for CD, these findings highlight a genetically determined subset of patients where CRP may not accurately reflect disease activity.
• Alternative biomarkers should be considered for disease activity assessment in CD patients with these specific CRP genetic variants.