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P824 Phenotypic and genetic markers of disease severity in a Maltese IBD cohort

J. Schembri*1, N. Pace2, N. Piscopo1, F. Degenhardt3, A. Franke3, P. Ellul1

1Mater Dei Hospital, Gastroenterology, Msida, Malta, 2University of Malta, Department of Biochemistry, Msida, Malta, 3Christian-Albrechts-University of Kiel, Institute of Clinical Molecular Biology, Kiel, Germany


Whilst most inflammatory bowel disease (IBD) treatment algorithms depend on disease severity classification, no formal validated definitions exist on what constitutes mild, moderate and severe ulcerative colitis (UC) and Crohn's disease (CD). Furthermore, the genetic architecture of disease severity may be distinct from that of disease susceptibility.


IBD patients were compared with eachother on the basis of disease severity. For the purpose of this study severe IBD was defined as current or previous use of anti-TNF agents or surgery. Genotyping was carried out on the Illumina Immunochip platform. Patients were characterised using the Montreal classification.


Using our definition for disease severity resulted in more CD patients being classified as severe.

Bar graph showing proportion of non-severe (white bars) to severe patients in both UC and CD.

Tables 1 and 2 summarise disease characteristics for UC (n = 109) and CD (n = 194) patients in our cohort. Mean illness durations for UC and CD were 11.9 years and 11.1 years.

Table 1. UC clinical characteristics and associations with disease severity.

Table 2. CD clinical characteristics and associations with disease severity.

Amongst these variables only disease duration (OR = 1.1) and hospitalisation (OR = 13) in UC and young age at diagnosis (OR = 1.1), disease behaviour (B2 OR = 6; B3 OR = 22) and location (L3 OR = 2) in CD remained significant after performing binary logistic regression.

Whilst several SNPs reached borderline association significance, 4 separate loci on chromosomes 2, 8, 14 and 16 are of special interest since they exhibit strong linkage disequilibrium between each other. Furthermore, these loci were different from the IBD susceptibility loci that emerged from another case–control association analysis comparing the same IBD patients to healthy controls.

Regional association plot for (a) CALCRL, (b) ZFAT, (c) C14orf2 and (d) PYCARD / FUS. 8d shows the strong linkage that exists between our typed SNPs and several polymorphisms occurring in integrin genes ITGAM, ITGAX and ITGAD.


IBD severity and susceptibility seem to be under the influence of different genetic factors and biological pathways. Whilst history of hospitalisation was the strongest determinant for severe UC, all domains of the Montreal classification contributed to CD severity. Further research on this subject requires international collaboration and agreement on what defines severe IBD.