Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease.
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.
Baldassano
Robert N
RN
Division of Gastroenterology and Nutrition, Abramson Research Center, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA.
Bradfield
Jonathan P
JP
Monos
Dimitri S
DS
Kim
Cecilia E
CE
Glessner
Joseph T
JT
Casalunovo
Tracy
T
Frackelton
Edward C
EC
Otieno
F George
FG
Kanterakis
Stathis
S
Shaner
Julie L
JL
Smith
Ryan M
RM
Eckert
Andrew W
AW
Robinson
Luke J
LJ
Onyiah
Chioma C
CC
Abrams
Debra J
DJ
Chiavacci
Rosetta M
RM
Skraban
Robert
R
Devoto
Marcella
M
Grant
Struan F A
SF
Hakonarson
Hakon
H
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
D015342:DNA Probes; C515500:IL23R protein, human; D018123:Receptors, Interleukin; D004247:DNA