Abstract
Crohn's disease (CD) is caused by a combination of environmental and genetic factors. It is not clear at present whether age of onset (AOO) is a random event or dictated by genotype or environmental factors. Mutations in the NOD2/caspase recruitment domains 15 (CARD15) and in the Toll-like receptor 4 (TLR4) gene have been associated with increased susceptibility for CD. We sought to determine whether single or multiple mutations in these genes are linked to earlier susceptibility for CD. A cohort of 189 patients with CD (82 pediatric onset, 107 adult onset) were genotyped for three disease-associated single-nucleotide polymorphisms (SNPs), one haplotype association (JW1-SNP5), and one background polymorphism (P268S) of the NOD2/CARD15 gene and for two SNPs of TLR4. Analysis of heterozygosity, homozygosity, alleles, and haplotypes of cohort on age or pediatric onset was performed. AOO ranged from 8 mo to 68 y. The presence of the three NOD2/CARD15 and two TLR4 mutations, the NOD2/CARD15 JW haplotype, compound heterozygosity, and homozygosity were not associated with AOO. Presence of P268S in the absence of known NOD2/CARD15 mutations was correlated with increasing age and adult onset of CD, whereas pediatric-onset disease was associated with male gender and the wild-type NOD2/CARD15 haplotype. Mutations in NOD2/CARD15 and TLR4 are not significantly associated with AOO in our population. Mutations that are not in linkage disequilibrium with the background mutation P268S of the NOD2/CARD15 gene probably play a more significant role in pediatric-onset disease.
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Abbreviations
- AOO:
-
age of onset
- CARD:
-
caspase recruitment domain
- CD:
-
Crohn's disease
- IBD:
-
inflammatory bowel disease
- LLR:
-
leucine-rich repeat
- LPS:
-
lipopolysaccharide
- SNP:
-
single-nucleotide polymorphism
- TLR4:
-
Toll-like receptor 4
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Leshinsky-Silver, E., Karban, A., Buzhakor, E. et al. Is Age of Onset of Crohn's Disease Governed by Mutations in NOD2/Caspase Recruitment Domains 15 and Toll-Like Receptor 4? Evaluation of a Pediatric Cohort. Pediatr Res 58, 499–504 (2005). https://doi.org/10.1203/01.PDR.0000175640.75468.D6
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DOI: https://doi.org/10.1203/01.PDR.0000175640.75468.D6
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