TY - JOUR
T1 - Association between genetic variants in the IL-23R gene and early-onset Crohn's disease
T2 - Results from a case-control and family-based study among Canadian children
AU - Amre, Devendra K.
AU - Mack, David
AU - Israel, David
AU - Morgan, Kenneth
AU - Lambrette, Philippe
AU - Law, Liliane
AU - Grimard, Guy
AU - Deslandres, Colette
AU - Krupoves, Alfreda
AU - Bucionis, Vytautas
AU - Costea, Irina
AU - Bissonauth, Vishnee
AU - Feguery, Houda
AU - D'Souza, Savio
AU - Levy, Emile
AU - Seidman, Ernest G.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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.
AB - BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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.
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U2 - 10.1111/j.1572-0241.2007.01661.x
DO - 10.1111/j.1572-0241.2007.01661.x
M3 - Article
C2 - 18047539
AN - SCOPUS:40949096976
VL - 103
SP - 615
EP - 620
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
SN - 0002-9270
IS - 3
ER -