Genetic susceptibility has a more important role in pediatric-onset Crohn's disease than in adult-onset Crohn's disease

Background: Genetic Susceptibility may play a more important role in the etiology of early-onset inflammatory bowel disease (IBD) than in late-onset 1131), and therefore pediatric-onset IBD patients can be expected to have a higher frequency of gene mutations. We aimed to determine genotypes and phenotypes of patients with pediatric-onset 113D, to compare them with those of patients with adult-onset]BD and with controls, and to identify genotype-phenotype associations. Methods: Polyinorphisms R702W, G908R, and 3020insC of CARD15 (caspase activating recruitment domain 15); Asp299GIy and Thr3991le of TLR4; -207G -> C, 1672C -> T (L503F), rs3792876, rs274551, rs272893, and rs273900 of SLC22A415; and 113G -> A as well as rs2289311, rsl270912, and rs2165047 of DLG5 (Drosophila discs large homologue 5) were assessed in 103 pediatric-onset and 696 adult-onset IBD patients. Phenotypic classification was based on disease localization and behavior. Results: Homozygosity for 3020insC in CARD15 was significantly higher in patients with pediatric-onset Crohn's disease (CD) than in patients with adUlt-onset CD (4.2% versus 0.6%, 95% confidence interval [CIl 1.2-42.0). Homozygosity for single-nucleotide polyinorphisin (SNP) rs3792876 in SLC22A415 was significantly higher in patients with pediatric-onset CD than in patients with adult-onset CD (6.1% versus 1.1%, P = 0.02). Polymorphisin 3020insC in CARD15 was associated with ileal involvement (1.9% versus 13.3%, CI 1.0-53.8) and a positive family history (6.1% versus 20%, Cl 1.2-9.0). DLG5 SNP rs2165047 was significantly associated with perianal disease (50% versus 21.2%, C1 1.4-4). Conclusions: Polymorphisins 3020insC in CARD15 and SNP rs3792876 in SLC22A415 occurred statistically significantly more often in patients with pediatric-onset CD than in patients with adult-onset CD. Polymorphisms 3020insC in CARD15 and SNP rs2165047 in DLG5 were associated with specific phenotypes in this pediatric-onset CD cohort.