Association Between Genetic Variants in the<i>IL</i>-<i>23R</i>Gene and Early-Onset Crohn's Disease: Results From a Case-Control and Family-Based Study Among Canadian Children

Amre, Devendra; Mack, David R.; Israel, David M.; Morgan, Kenneth; Lambrette, Philippe; Law, Liliane; Grimard, Guy; Deslandres, Colette; Krupoves, Alfreda; Bucionis, Vytautas; Costea, Irina; Bissonauth, Vishnee; Feguery, Houda; D’Souza, Savio; Lévy, Émile; Seidman, Ernest G.

doi:10.1111/j.1572-0241.2007.01661.x

Cited by 58 publications

(47 citation statements)

References 28 publications

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“…Our results provide an independent confirmation of the association between the candidate genetic variation IL23R and cd (10), and reinforce the role of this new polymorphism as a genetic determinant of CD. Further research is necessary to understand how IL23R contributes to disease susceptibility in CD.…”

Section: Discussionsupporting

confidence: 72%

“…The role attributed to IL23R is not to actively induce the differentiation of naive T cells, but rather to stabilise the already differentiated Th17 sub-population (9). evidence for genetic risk factors for CD is well established with respect to the NOD2)/CARD15 gene (10). In 1996, Hugot et al discovered NOD2/CARD15, the first gene identified to be associated with IbD (11).…”

Section: Introductionmentioning

confidence: 99%

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IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes

Lauriola

Ugolini²,

Rivetti³

et al. 2011

Int J Mol Med

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Abstract. Recent genomic research has identified interleukin-23 receptor (IL23R), nucleotide-binding oligomerization domain containing 2 caspase-activation recruitment domain 15 (NOD2/CARD15), autophagy related 16-like 1 (ATG16L1) and paired-like homeobox 2b (PHOX2B) as susceptibility loci for Crohn's Disease (CD). Our aim was to investigate these gene variants in a group of CD patients and to analyse the correlation to sub-phenotypes such as gender, smoking habits, disease behaviour at diagnosis, severity of disease and extra-intestinal manifestations. Nineteen patients with CD and 20 healthy controls were included in the study. The gene variants IL23R rs7517847 and rs11209026, NOD2/CARD15 rs2066845, PHOX2B rs16853571, ATG16L1 rs2241879 and rs2241880 were genotyped by PCR followed by sequencing. The frequency of the G risk allele of IL23R rs7517847 was found to be increased in patients with CD (42%) compared to that in control subjects (20%) [odds ratio (OR), 2.9; 95% confidence interval [CI], 1.06-7.9; P=0.03]. In addition, the homozygous condition GG was also associated with CD (OR, 8.70; 95% CI, 0.9-81.6; P=0.038). The analysis of correlation of genotype to sub-phenotypes showed an association of ATG16L1 rs2241879 with the lack of extra-intestinal manifestations (OR, 0.03; 95% CI, 0.002-0.45; P=0.006), and the patients defined as non-smokers displayed an increased frequency of the risk allele C (P=0.03). The present study confirms the association of the heterozygous and homozygous IL23R rs7517847 variant with CD and suggests an additive effect of smoking to the ATG16L1 rs2241879 C risk allele SNP, in the context of the multifactorial model established for the development of CD and a protective effect of the same allele against extra-intestinal manifestations.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes

Lauriola

Ugolini²,

Rivetti³

et al. 2011

Int J Mol Med

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“…Moreover, we found no statistical evidence for epistatic interaction between IL23R, ATG16L1, OCTN1/2, and CARD15 genes. Since our cohort also included a large number of pediatric cases (368 diagnosed at age < 19 years), this study confirmed that the rs2241880 polymorphism in the ATG16L1 [34,37] gene and the rs7517847, rs11209026 polymorphisms in the IL23R gene [22,25,[27][28][29][30] also influence susceptibility to CD in pediatric-onset patients, at allele and genotype frequencies comparable to that seen in adults.…”

Section: Discussionmentioning

confidence: 52%

“…The association of this variant appeared statistically independent from Arg381Gln and not in linkage disequilibrium (r 2 = 0.03) [15] . A large number of replications in adult- [20][21][22][23][24] and pediatric-onset [25][26][27][28][29] cohorts have been reported, but no significant association with specific CD sub-phenotype has been identified. Moreover, an association with UC has also been observed [23,24,28,30,31] .…”

Section: Introductionmentioning

confidence: 99%

Replication of interleukin 23 receptor and autophagyrelated 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy

Latiano¹,

Palmieri²,

Valvano³

et al. 2008

WJG

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RESULTS:The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced significantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult-and pediatric-onset subsets in our study population.

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“…Multiple SNPs showing an association with both CD and UC have been identified in the IL23R gene by recent GWA studies. These findings were meanwhile replicated in a number of adult [13,45] and paediatric [46][47][48][49][50] cohorts. However, no associations were seen in a Japanese cohort [51].…”

Section: Discussionmentioning

confidence: 56%

Replication of Identified Inflammatory Bowel Diseases Genetic Associations: A Case–Control Study in the Tunisian Population

Bouzid¹

2013

J Clin Cell Immunol

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Inflammatory bowel diseases (IBD) -Crohn's disease (CD) and ulcerative colitis (UC) -are chronic gastrointestinal inflammatory disorders with a complex genetic background. A genome wide association scan by the Welcome Trust Case Control Consortium (WTCCC) recently identified several novel susceptibility loci. We performed a replication study in 107 IBD patients (39 CD and 68 UC) and 162 controls. In total, 19 single nucleotide polymorphisms (SNPs) from previously identified susceptibility genes PTPN11, TNF α, IL23R, PTPN2, PTPN22, IL2 and IL10 were studied. In UC, we confirmed the association with PTPN2 (rs254215, GG, P=0.013, P corr =0.039; OR= 6.23 (1.18; 32.95)). In CD, we confirmed a marginal association with ((rs11066320, GG, P=0.018, P corr =0.054, OR= 0.4 (0.19; 0.82)). No significant association was found at the allele and genotype levels of SNPs in TNF α, IL23R, PTPN22, IL2, and IL10. However, on the haplotype analysis the AG haplotype of TNFα was more frequent in CD patients compared to controls (23.1% vs. 13.7%; P = 0.039; OR= 1.89 (1.02; 3.5)). The PTPN11 ATG haplotype was also more frequent in CD patients compared to controls (32.1% vs 21.3%; P = 0.04; OR= 1.75 (1.01; 3.01). These results reveal limited replication in Tunisian population and indicate differences in genetic architecture between populations.

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Association Between Genetic Variants in theIL-23RGene and Early-Onset Crohn's Disease: Results From a Case-Control and Family-Based Study Among Canadian Children

Abstract: 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.

Cited by 58 publications

References 28 publications

IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes

IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes

Replication of interleukin 23 receptor and autophagyrelated 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy

Replication of Identified Inflammatory Bowel Diseases Genetic Associations: A Case–Control Study in the Tunisian Population

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