IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease

✍ Scribed by Marla C. Dubinsky; Dai Wang; Yoana Picornell; Iwona Wrobel; Lirona Katzir; Antonio Quiros; Debra Dutridge; Ghassan Wahbeh; Gary Silber; Ron Bahar; Emebet Mengesha; Stephan R. Targan; Kent D. Taylor; Jerome I. Rotter

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 83 KB
• Volume: 13
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20126

✦ Synopsis

Background:

The il-23 receptor (il-23r) has been found to be associated with small bowel crohn's disease (cd) in a whole genome association study. specifically, the rare allele of the r381q single nucleotide polymorphism (snp) conferred protection against cd. it is unknown whether il-23r is associated with ibd in children. the aim was to examine the association of il-23r with susceptibility to ibd in pediatric patients.

Methods:

Dna was collected from 609 subjects (151 cd and 52 ulcerative colitis [uc] trios). trios were genotyped for the r381q snp of the il-23r gene and snp8, snp12, snp13, of the card15 gene using taqman. the transmission disequilibrium test (tdt) was used for association to disease using genehunter 2.0.

Results:

The rare allele of r381q snp was present in 2.7% of cd and 2.9% uc probands. the card15 frequency was 31.5% (cd) and 18% (uc). the il-23r allele was negatively associated with inflammatory bowel disease (ibd): the r381q snp was undertransmitted in children with ibd (8 transmitted [t] versus 27 untransmitted [ut]; p = 0.001). this association was significant for all cd patients (6 t versus 19 ut; p = 0.009), especially for non-jewish cd patients (2 t versus 17 ut; p = 0.0006). tdt showed a borderline association for uc (2 t versus 8 ut; p = 0.06). as expected, card15 was associated with cd in children by the tdt (58 t versus 22 ut p = 0.00006), but not with uc.

Conclusions:

The protective il-23r r381q variant was particularly associated with cd in non-jewish children. thus, the initial whole genome association study based on ileal cd in adults has been extended to the pediatric population and beyond small bowel cd.