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Review
. 2010 May;24(5):297-302.
doi: 10.1155/2010/480458.

Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn's disease

Lynn Cotterill  1 , Debbie Payne, Scott Levinson, John McLaughlin, Emma Wesley, Mark Feeney, Hilary Durbin, Simon Lal, Alistair Makin, Simon Campbell, Stephen A Roberts, Catherine O'Neill, Cathryn Edwards, William G Newman
Affiliations
Review

Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn's disease

Lynn Cotterill et al. Can J Gastroenterol. 2010 May.

Abstract
in English, French

Background/objective: Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn's disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed.

Methods: British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively.

Results: In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively).

Conclusion: The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population.

HISTORIQUE ET OBJECTIF :: Des variantes du gène du récepteur de l’interleukine 23 (IL23R) et du gène 1 de type 16 lié à l’autophagie (ATG16L1) s’associent à une augmentation du risque de maladie de Crohn (MC). Ces deux gènes ont été repérés par balayages d’association sur tout le génome, et des études subséquentes ont validé ces associations. Pour évaluer l’ampleur de l’effet de ces variantes, les chercheurs ont procédé à une étude d’association cas-témoins et à une méta-analyse.

MÉTHODOLOGIE :: Des sujets britanniques blancs atteints d’une maladie inflammatoire de l’intestin (MII) (n=500) et 877 sujets témoins appariés selon l’ethnie ont subi un génotypage pour déceler les variantes associées à la maladie dans les gènes IL23R et ATG16L1. De plus, les chercheurs ont effectué des méta-analyses de 12 991 patients et 14 598 sujets-témoins ainsi que de 11 909 patients et 15 798 sujets-témoins à partir de données indépendantes pour déceler les associations entre les variantes des gènes IL23R et ATG16L1 et la MC, respectivement.

RÉSULTATS :: Dans la présente cohorte, les deux variantes de susceptibilité ont révélé des associations hautement significatives, incluant les gènes IL23R (rs11209026, P=0,0006; RRR 0,37; 95 % IC 0,21 à 0,67) et ATG16L1 (rs2241880, P=0,0017; RRR 1,36; 95 % IC 1,12 à 1,66). La méta-analyse fondée sur le modèle d’essais aléatoires a révélé des effets combinés similaires pour le rs11209026 (n=26, RRR 0,41; 95 % IC 0,37 à 0,46) et le rs2241880 (n=25, RRR 1,33; 95 % IC 1,28 à 1,39). Les chercheurs n’ont constaté aucune interaction statistiquement significative d’un gène à l’autre entre les variantes du domaine de recrutement de la caspase (CARD15) et les polymorphismes des gènes IL23R ou ATG16L1 (P=0,44 et P=0,24, respectivement).

CONCLUSION :: La présente cohorte et la présente analyse fournissent des données probantes solides selon lesquelles en plus du CARD15, les polymorphismes des gènes IL23R et ATG16L1 modifient la susceptibilité à la MC et que ces effets sont constants entre toutes les populations d’origine européenne. Cependant, seul le gène ATG16L1 est pertinent pour la maladie inflammatoire de l’intestin au sein de la population asiatique.

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Figures

Figure 1)
Figure 1)
Meta-analysis of the random effects model of the association between the autophagy-related 16-like 1 (ATG16L1) variant and Crohn’s disease in 25 individual studies. ES Epidemiological study
Figure 2)
Figure 2)
Meta-analysis of the random effects model of the association between the interleukin-23 receptor (IL23R) variant and Crohn’s disease in 26 individual studies. ES Epidemiological study
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