The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients

TY - JOUR

T1 - The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients

AU - Riis, Lene

AU - Vind, Ida

AU - Vermeire, Severine

AU - Wolters, Frank

AU - Katsanos, Kostas

AU - Politi, Patrizia

AU - Freitas, João

AU - Mouzas, Ioannis A

AU - O'Morain, Colm

AU - Ruiz-Ochoa, Victor

AU - Odes, Selwyn

AU - Binder, Vibeke

AU - Munkholm, Pia

AU - Moum, Bjørn

AU - Stockbrügger, Reinhold

AU - Langholz, Ebbe

AU - European Collaborative Study Group on Inflammatory Bowel Disease

PY - 2007/1

Y1 - 2007/1

N2 - BACKGROUND AND AIM: 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.CONCLUSION: 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.

AB - BACKGROUND AND AIM: 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.CONCLUSION: 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.

KW - Antibodies, Antineutrophil Cytoplasmic/blood

KW - Antibodies, Fungal/blood

KW - Cohort Studies

KW - Colitis, Ulcerative/genetics

KW - Crohn Disease/genetics

KW - Europe

KW - Gene Frequency

KW - Humans

KW - Mutation

KW - Nod2 Signaling Adaptor Protein/genetics

KW - Polymorphism, Single Nucleotide

KW - Saccharomyces cerevisiae/immunology

KW - Toll-Like Receptor 4/genetics

U2 - 10.1002/ibd.20047

DO - 10.1002/ibd.20047

M3 - Journal article

C2 - 17206636

SN - 1078-0998

VL - 13

SP - 24

EP - 32

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

IS - 1

ER -