Association between genetic variants in the IL-23R gene and early-onset Crohn's disease: results from a case-control and family-based study among Canadian children.
OBJECTIVE
Interleukin (IL)-23 is a key regulator of inflammation and influences the activities of T-helper 17 (Th-17) lymphocytes. Recent reports indicate that variants in the gene coding for its receptor (IL-23R) are strongly associated with Crohn's disease (CD). We investigated whether DNA variants in the IL-23R gene determine susceptibility for CD in Canadian children.


METHODS
A case-control and case-parent trio design was implemented at three pediatric centers across Canada. Cases of CD (</=20 yr) along with their parents and controls were recruited. DNA samples were collected and genotyped for 10 single nucleotide polymorphisms (SNPs) in the IL-23R gene and three common SNPs in the CARD15 gene. Transmission disequilibrium-based tests were applied to the case-parent data and logistic regression models to the case-control data to study the association between the SNPs and CD.


RESULTS
A total of 259 CD cases, 139 controls, and 232 families (167 trios and 65 dyads) were studied. The mean age at diagnosis was 13.3 yr (range 2.6-20 yr). The majority of the patients were Caucasian. Case-control analysis revealed significant associations with three SNPs (rs1004819, rs7517847, and rs11209026 [R381Q]) and borderline nonsignificant associations with three other SNPs (rs10489629, rs10889697, and rs11465804) in the IL-23R gene. Having any CARD15 variant was associated with a significant risk for CD (P < 0.0001). Analyses of case-parent data confirmed the findings from the case-control analysis including significant associations with the R381Q SNP (P= 0.002). The common variant in this SNP conferred risk for CD. These associations were largely independent of the CARD15 gene.


CONCLUSIONS
Our findings confirm recently reported genome-wide associations between the IL-23R gene and CD. They suggest that the gene is also associated with pediatric-onset CD among Canadian children.
Department of Paediatrics, University of Montreal, Montreal, Canada, and Research Centre, Sainte-Justine Hospital, Montreal, Canada.
Devendra K
DK
Amre
David
D
Mack
David
D
Israel
Kenneth
K
Morgan
Philippe
P
Lambrette
Liliane
L
Law
Guy
G
Grimard
Colette
C
Deslandres
Alfreda
A
Krupoves
Vytautas
V
Bucionis
Irina
I
Costea
Vishnee
V
Bissonauth
Houda
H
Feguery
Savio
S
D'Souza
Emile
E
Levy
Ernest G
EG
Seidman
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002170:Canada; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*
C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin