The American journal of gastroenterology · 2007
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.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Amre Devendra K, Mack David, Israel David, Morgan Kenneth, Lambrette Philippe, Law Liliane, Grimard Guy, Deslandres Colette, Krupoves Alfreda, Bucionis Vytautas, Costea Irina, Bissonauth Vishnee, Feguery Houda, D'Souza Savio, Levy Emile, Seidman Ernest G
Аннотация
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.
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.