title: Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease.
abstract: OBJECTIVE
  Recently an association was shown between the single nucleotide polymorphism (SNP), rs11209026, within the interleukin-23 receptor (IL23R) locus and Crohn's disease (CD) as a consequence of a genome-wide association study of this disease in adults. We examined the effects of this and other previously reported SNPs at this locus with respect to CD in children.
  
  
  METHODS
  By using data from our ongoing genome-wide association study in our cohort of 142 pediatric CD patients and 281 matched controls, we investigated the association of the previously reported SNPs at the IL23R locus with the childhood form of this disease.
  
  
  RESULTS
  By using the Fisher exact test, the minor allele frequency of rs11209026 in the patients was 1.75%, whereas it was 6.61% in the controls, yielding a protective odds ratio (OR) of 0.25 (95% confidence interval, 0.10-0.65; 1-sided P = 9.2 x 10(-4)). Furthermore, of all the SNPs previously reported, rs11209026 was associated the most strongly. A subsequent family based association test (which is more resistant to population stratification) with 65 sets of trios derived from our initial patient cohort yielded significant association with rs11209026 in a transmission disequilibrium test (1-sided P = .0017). In contrast, no association was detected to the caspase-recruitment domain 15 gene for the inflammatory bowel disease phenotype.
  
  
  CONCLUSIONS
  The OR of the IL23R variant in our pediatric study is highly comparable with that reported previously in a non-Jewish adult inflammatory bowel disease case-control cohort (OR, 0.26). As such, variants in the IL23R gene confer a similar magnitude of risk of CD to children as for their adult counterparts.
authors.affiliation: Division of Gastroenterology and Nutrition, Abramson Research Center, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradfield
authors.forename: Dimitri S
authors.initials: DS
authors.lastname: Monos
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Kim
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Tracy
authors.initials: T
authors.lastname: Casalunovo
authors.forename: Edward C
authors.initials: EC
authors.lastname: Frackelton
authors.forename: F George
authors.initials: FG
authors.lastname: Otieno
authors.forename: Stathis
authors.initials: S
authors.lastname: Kanterakis
authors.forename: Julie L
authors.initials: JL
authors.lastname: Shaner
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Smith
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Eckert
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Robinson
authors.forename: Chioma C
authors.initials: CC
authors.lastname: Onyiah
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Abrams
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.forename: Robert
authors.initials: R
authors.lastname: Skraban
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
mesh_terms: D000483:Alleles; D002648:Child; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D015342:DNA Probes; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D015342:DNA Probes; C515500:IL23R protein, human; D018123:Receptors, Interleukin; D004247:DNA