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 IBD, 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 IBD, to compare them with those of patients with adult-onset IBD and with controls, and to identify genotype-phenotype associations.


METHODS
Polymorphisms R702W, G908R, and 3020insC of CARD15 (caspase activating recruitment domain 15); Asp299Gly and Thr399Ile of TLR4; -207G-->C, 1672C-->T (L503F), rs3792876, rs274551, rs272893, and rs273900 of SLC22A4/5; and 113G-->A as well as rs2289311, rs1270912, 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 [CI] 1.2-42.0). Homozygosity for single-nucleotide polymorphism (SNP) rs3792876 in SLC22A4/5 was significantly higher in patients with pediatric-onset CD than in patients with adult-onset CD (6.1% versus 1.1%, P=0.02). Polymorphism 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%, CI 1.2-9.0). DLG5 SNP rs2165047 was significantly associated with perianal disease (50% versus 21.2%, CI 1.4-4).


CONCLUSIONS
Polymorphisms 3020insC in CARD15 and SNP rs3792876 in SLC22A4/5 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.
de Ridder
Lissy
L
Department of Pediatric Gastroenterology, VU University Medical Center, and Department of Pediatric Gastroenterology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands. l.deridder@vumc.nl
Weersma
Rinse K
RK
Dijkstra
Gerard
G
van der Steege
Gerrit
G
Benninga
Marc A
MA
Nolte
Ilja M
IM
Taminiau
Jan A J M
JA
Hommes
Daniël W
DW
Stokkers
Pieter C F
PC
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C114461:DLG5 protein, human; D008565:Membrane Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D025521:Tumor Suppressor Proteins