Jakobsen, C3; Cleynen, I4; Andersen, P S5; Vermeire, S6; Munkholm, P7; Paerregaard, A1; Wewer, Anne Vibeke1
1 Department of Pediatrics, Amager and Hvidovre Hospital, The Capital Region of Denmark2 Gastroenterology, Herlev and Gentofte Hospital, The Capital Region of Denmark3 Thoraxkirurgisk Klinik, Hjertecentret Rigshospitalet, Rigshospitalet, The Capital Region of Denmark4 University of Leuven5 Statens Serum Institut6 Leuven University Hospital7 Department of Gastroinstestinal Surgery, Nordsjællands Hospital, The Capital Region of Denmark
AIM: To investigate the association between known inflammatory bowel disease (IBD)-associated genetic variants and development of paediatric IBD, and specific clinical sub-phenotypes. MATERIAL AND METHODS: In this case-control study we included IBD patients <18years of age at diagnosis from the Danish National Patient Registry and healthy children <18years of age were randomly selected from the Danish Central Office of Civil Registration. The latter had filled out a questionnaire regarding health status, and DNA was obtained from blood samples and the buccal mucosa. Patient files were retrieved and clinical information was extracted. DNA was obtained from Guthrie cards from the Danish National Neonatal Screening Biobank (PKU-biobanken) at Statens Serum Institut and from blood samples. RESULTS: A total of 588 IBD patients (244 Crohn's disease (CD), 318 ulcerative colitis (UC) and 26 IBD-unclassified (IBDU)) and 543 healthy controls were included. We found an association between CD and rs22411880 (ATG16L1, odds ratio (OR)=1.7 [1.1-1.7], p=0.003), rs5743289 (NOD2, OR=1.4 [1.1-1.9], p=0.009) and the paediatric specific rs1250550 (ZMIZ1, OR=0.7 [0.5-0.9], p=0.01). None of the investigated 41 SNPs were associated with disease localisation, medical treatment or surgery after correcting for multiple analyses. CONCLUSION: We found an association between CD and three previously published genetic variants and replicated the association with the paediatric specific ZMIZ1 gene. No Bonferroni corrected significant genotype-phenotype associations were found. For future studies aimed at finding predictors for disease course in (paediatric) IBD, it will be worthwhile to include a combination of genetic, clinical and serological markers.
Journal of Crohn's and Colitis, 2014, Vol 8, Issue 7, p. 678-85