Genetic profile of patients with early onset inflammatory bowel disease

Girardelli M1, Basaldella F1, Paolera SD1, Vuch J1, Tommasini A1, Martelossi S1, Crovella S2, Bianco AM3. Gene. 2018 Mar 1;645:18-29. doi: 10.1016/j.gene.2017.12.029. Epub 2017 Dec 15.
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1 Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'istria 65, Trieste, Italy.

2 Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'istria 65, Trieste, Italy; University of Trieste, Piazzale Europa, 1, Trieste 34128, Italy.

3 Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'istria 65, Trieste, Italy. Electronic address: annamonicarosaria.bianco@burlo.trieste.it.


Inflammatory Bowel disease (IBD) is a widespread pathological condition with clinical heterogeneity and with different levels of severity. Although IBD usually occurs in young adults, onset in childhood and infancy are described in patients within the 10th and second year of age. By genome-wide association studies and meta-analysis, several genetic loci have been identified associated with an increased risk of developing IBD in Western populations with variants that may alter the normal mucosal immunity in the gastrointestinal tract. The clinical complexity and the heterogeneity of the IBD phenotype probably reflect the presence of genetic heterogeneity where different genes or combinations of them may be involved, together with environmental factors. We hypothesized that patients with early onset IBD could have either more severe genetic variants in genes associated with IBD or multiple variants in different genes. Under the multifactorial diseases is crucial to consider the small contribution of a single variant in all not only to other small variations in the same gene but also in different genes belonging to the same pathway. We performed direct gene sequencing looking for 94 variations in NOD2, ATG16L1, IL23R, IL10R, IL10 and XIAP genes previously shown as correlated with IBD both in multifactorial and in Mendelian models. All variants identified are known in literature as being associated with IBD except for three variants in the genes NOD2, IL10 and IL10RB that even though present in online databases have never been involved in association studies on IBD patients. Moreover, we coupled genetic variants identification with an accurate "in silico" analysis to verify their predictive impact on the protein structure and function. The in-silico prediction of these variants results as benign therefore even if they exhibit a very low frequency in control population being benign, they cannot be considered pathogenic as monogenic disease but fall within the multifactorial range. The variants identified in our study partially reflect the association data described in the literature but there are no significant differences with the onset of disease (VEO vs EO-IBD).

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