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Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn’s disease
  1. H Peeters1,
  2. B Vander Cruyssen2,
  3. D Laukens3,
  4. P Coucke4,
  5. D Marichal1,
  6. M Van Den Berghe2,
  7. C Cuvelier5,
  8. E Remaut3,
  9. H Mielants2,
  10. F De Keyser2,
  11. M D Vos1
  1. 1Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
  2. 2Department of Rheumatology, Ghent University Hospital
  3. 3Department of Molecular Biomedical Research-VIB, Ghent University and Flanders Interuniversity Institute for Biotechnology (VIB), Ghent
  4. 4Centre for Medical Genetics, Ghent University Hospital
  5. 5Department of Pathology, Ghent University Hospital
  1. Correspondence to:
    Dr Harald Peeters
    Department of Gastroenterology, Ghent University Hospital, B-9000 Ghent, Belgium;


Background: Sacroiliitis is a common extraintestinal manifestation of Crohn’s disease but its association with the HLA-B27 phenotype is less evident. Polymorphisms in the CARD15 gene have been linked to higher susceptibility for Crohn’s disease. In particular, associations have been found with ileal and fibrostenosing disease, young age at onset of disease, and familial cases.

Objectives: To investigate whether the presence of sacroiliitis in patients with Crohn’s disease is linked to the carriage of CARD15 polymorphisms.

Methods: 102 consecutive patients with Crohn’s disease were clinically evaluated by a rheumatologist. Radiographs of the sacroiliac joints were taken and assessed blindly by two investigators. The RFLP-PCR technique was used to genotype all patients for three single nucleotide polymorphisms (SNP) in the CARD15 gene. Every SNP was verified by direct sequencing. The HLA-B27 phenotype was determined.

Results: Radiological evidence of sacroiliitis with or without ankylosing spondylitis was found in 23 patients (23%), of whom only three were HLA-B27 positive. In contrast, 78% of patients with sacroiliitis carried a CARD15 variant v 48% of those without sacroiliitis (p = 0.01; odds ratio 3.8 (95% confidence interval, 1.3 to 11.5)). Multivariate analysis (logistic regression) showed that the association between sacroiliitis and CARD15 polymorphisms was independent of other CARD15 related phenotypes (ileal and fibrostenosing disease, young age at onset of disease, familial Crohn’s disease) (p = 0.039).

Conclusions: CARD15 variants were identified as genetic predictors of Crohn’s disease related sacroiliitis. An association was demonstrated between these polymorphisms and an extraintestinal manifestation of Crohn’s disease.

  • AS, ankylosing spondylitis
  • CARD, caspase activation and recruitment domain
  • IBD, inflammatory bowel disease
  • RFLP-PCR, restriction fragment length polymorphism polymerase chain reaction
  • SNP, single nucleotide polymorphism
  • CARD15
  • Crohn’s disease
  • HLA B27
  • sacroiliitis

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