P673 ATG16L1 and IRGM1 polymorphisms in pediatric Crohn's disease: correlation with phenotype

Abstract

Background: Genome wide association studies (GWAS) find a significative correlation between several single nucleotide polymorphisms (SNPs) involved in autophagy and the occurrence of Crohn’s disease (CD) risk both in children and in adult patients. However, few incomplete and discordant evidences about the correlation of these SPNs and a specific phenotype of CD have been described in pediatric patients. Our purpose is to investigate the relationship between the autophagy gene variants of ATG16L1 and IRGM1 and clinical features in our cohort of children affected by CD. Methods: Eighty consecutive children with CD (mean age: 14.8±4.6 years) were enrolled in our study. Genotyping for ATG16L1 (rs2241880) and IRGM1 (rs13361189; rs4958847) was performed in all patients. Phenotypic informations including disease localization and behaviour stratified according to the Paris classification were collected. Moreover, phenotype data regarding medical therapy, relapses, surgery recurrences and laboratoristic inflammation parameters were analysed. Results: CD patients with the homozygous variant for the ATG16L1 (var) allele showed a significant tendence to change the clinical behaviour switching to a stenosing or fistolizing phenotype during the course of disease compared with children carrying the homozygous protective allele of ATG16L1 (wt) and heterozygous patients (het) (p = 0.05). In addition, the presence of ATG16L1 var resulted to be associated with a major recurrence of clinical relapses and an earlier introduction of immunosuppressants (p = 0.006 and p = 0.04 respectively). However, ATG16L1 var seems not to be related to a positive family history and extraintestinal manifestations (p = 0.4 and p = 0.5) and resulted to be protective for perianal disease, which was more frequent in het and wt patients (p = 0.06). Patients carrying ATG16L1 var were more frequently males (p = 0.07) and presented a signifcant higher value of fecal calprotectin at diagnosis (p = 0.007). IRGM1 rs4958847 homozygous variant was correlated with a trend toward statistical significance regards to a positive family history (p = 0.078) and the presence of extraintestinal manifestations (p = 0.08). Conclusions: CD patients carrying ATG16L1 var seem to be characterized by a more aggressive disease course, including changes in clinical behaviour, a higher number of relapses and an earlier use of immunosuppressants. IRGM1 rs4958847 variant gene is correlated with a positive family history and with extraintestinal manifestations.