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Radiological sacroiliitis is linked with CARD15 gene polymorphisms in patients with Crohn's disease


Sacroiliitis (SI) is a common extraintestinal manifestation of Crohn's disease (CD). In contrast to idiopathic ankylosing spondylitis (AS), its association with HLA-B27 is less evident. Mutations in the CARD15 gene are recently identified as susceptiblity genes for CD. The CARD15 gene encodes the intracellular NOD2 receptor and should play an important role in innate immunity. Studies on associated disease phenotypes revealed a predisposition for ileal localization, early onset of disease, familial cases and fibrostenosing disease. We recently described a higher prevalence of CARD15 variants in a subgroup of spondyloarthropathy patients with chronic gut inflammation, which are prone to evolution to CD.


The present study evaluated whether CARD15 polymorphisms are associated with sacroiliitis in patients with CD.


One hundred and two consecutive CD patients were clinically evaluated by a rheumatologist. Radiographs of sacroiliac joints were performed and blindly scored by two investigators. RFLP-PCR technique was used to genotype all patients for three single nucleotide polymorphisms in the CARD15 gene. Every SNP was verified by direct sequencing. HLA-B27 phenotype was determined.


Radiological evidence of SI with or without AS was present in 23 patients (23%). Of patients with SI 78% carried a CARD15 variant, versus 48% of patients without SI (P = 0.011; OR 3.8, 95% CI 1.3–11.5). A logistic regression analysis with SI as dependent variable and CARD15, HLA-B27, famililial cases, need for resection surgery, age of diagnosis and ileal disease as covariates showed that only carriage of CARD15 variants was a significant predictor of SI (P = 0.035).


This result suggests that carriage of CARD15 variants is a genetic marker for CD related SI, independent of HLA-B27 or other CARD15 related phenotypes.

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Cruyssen, B.V., Peeters, H., Laukens, D. et al. Radiological sacroiliitis is linked with CARD15 gene polymorphisms in patients with Crohn's disease. Arthritis Res Ther 6 (Suppl 1), 76 (2004).

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