The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients.
OBJECTIVE
The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort.


METHODS
Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files.


RESULTS
Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype.


CONCLUSIONS
The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.
Riis
Lene
L
Department of Medical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark. l.riis@dadlnet.dk
Vind
Ida
I
Vermeire
Severine
S
Wolters
Frank
F
Katsanos
Kostas
K
Politi
Patrizia
P
Freitas
João
J
Mouzas
Ioannis A
IA
O'Morain
Colm
C
Ruiz-Ochoa
Victor
V
Odes
Selwyn
S
Binder
Vibeke
V
Munkholm
Pia
P
Moum
Bjørn
B
Stockbrügger
Reinhold
R
Langholz
Ebbe
E
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000908:Antibodies, Fungal / Q000097:blood; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology*; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology; D005060:Europe; D005787:Gene Frequency; D006801:Humans; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012441:Saccharomyces cerevisiae / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D019268:Antibodies, Antineutrophil Cytoplasmic; D000908:Antibodies, Fungal; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4