title: IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease.
abstract: 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.
authors.affiliation: Department of Pediatrics, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. dubinskym@csmc.edu
authors.forename: Marla C
authors.initials: MC
authors.lastname: Dubinsky
authors.forename: Dai
authors.initials: D
authors.lastname: Wang
authors.forename: Yoana
authors.initials: Y
authors.lastname: Picornell
authors.forename: Iwona
authors.initials: I
authors.lastname: Wrobel
authors.forename: Lirona
authors.initials: L
authors.lastname: Katzir
authors.forename: Antonio
authors.initials: A
authors.lastname: Quiros
authors.forename: Debra
authors.initials: D
authors.lastname: Dutridge
authors.forename: Ghassan
authors.initials: G
authors.lastname: Wahbeh
authors.forename: Gary
authors.initials: G
authors.lastname: Silber
authors.forename: Ron
authors.initials: R
authors.lastname: Bahar
authors.forename: Emebet
authors.initials: E
authors.lastname: Mengesha
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007223:Infant; D007585:Jews / Q000235:genetics; D015810:Linkage Disequilibrium; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*
chemical_list: C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin; D005973:Glutamine