Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease.
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.


OBJECTIVE
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.
Peeters
H
H
Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium. harald.peeters@UGent.be
Vander Cruyssen
B
B
Laukens
D
D
Coucke
P
P
Marichal
D
D
Van Den Berghe
M
M
Cuvelier
C
C
Remaut
E
E
Mielants
H
H
De Keyser
F
F
Vos
M D
MD
D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D003424:Crohn Disease / Q000150:complications / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000032:analysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D011859:Radiography; D012446:Sacroiliac Joint / Q000000981:diagnostic imaging; D013166:Spondylitis / Q000000981:diagnostic imaging / Q000235:genetics*
D002352:Carrier Proteins; D015796:HLA-B27 Antigen; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein