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

Christopher J Moran1,2, Jess L Kaplan1,2, Harland S Winter1,2

  • 1Division of Pediatric Gastroenterology, Hepatology, and Nutrition, MassGeneral Hospital for Children, Boston, Massachusetts.

Inflammatory Bowel Diseases
|May 3, 2018
PubMed

Insights

Genetic variants in C-reactive protein (CRP) can limit CRP elevations during Crohn's disease (CD) flares. This impacts CRP's reliability as a biomarker in some CD patients.

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.
Abstract

Keywords:
C-reactive proteinCrohn’s diseasegenetics

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