NOD2/CARD15 and IL23R genetic variability in 204 Algerian Crohn's disease

Meddour, Yanis; Chaib, Samia; Bousseloub, A.; Kaddache, N.; Kécili, L.; Gamar, L.; Nakkemouche, Mhamed; Djidjik, Réda; Abbadi, Mohamed Chérif; Charron, Dominique; Boucekkine, T.; Tamouza, Ryad

doi:10.1016/j.clinre.2014.02.003

Cited by 12 publications

(11 citation statements)

References 32 publications

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“…A total of 33 articles, 20,23,24,[27][28][29][30][31]33,35,37,38,[40][41][42]44,47,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] involving 8110 cases and 11,900 controls (Table 2), were included to the meta-analysis regarding the genetic effect of the The overall genetic risk suggested significant protection for the AA genotype (OR G ¼ 0.46; 95% CI, 0.41-0.52). The subgroup analysis on adults 16 20,23,24,[27][28][29][30]33,35,37,38,41,[47][48][49][50]…”

Section: Il23r Variant Rs11209026 and Disease Susceptibilitymentioning

confidence: 99%

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ATG16L1 and IL23R Variants and Genetic Susceptibility to Crohnʼs Disease

Grigoras

Ziakas

Jayamani

et al. 2015

Inflammatory Bowel Diseases

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Background: Autophagy and regulation of IL-23 signaling pathways have been implicated in the pathogenesis of Crohn's disease (CD). We studied the mode of inheritance and reviewed the association of 2 polymorphic variants of ATG16L1 and IL23R with CD.Methods: We searched the PubMed and ISI Web of Science databases (up to May 2014) for pertinent articles. We included all studies that had a casecontrol design, with cases having CD and controls being healthy and reported full genotype frequencies for the ATG16L1 and/or IL23R variant of interest. We quantified the relative genetic risk using the model-free approach of the generalized odds ratio metric (OR G ) and reported 95% precision estimates. Also, we explored the mode of inheritance using the degree of dominance h-index.Results: Fifty-one studies fulfilled these requirements and were included in the analysis. These studies involved 12,762 patients and 16,735 controls evaluating the association of ATG16L1 (rs2241880 p.Thr300Ala) and 8110 patients and 11,900 controls evaluating the association of IL23R (rs11209026 p. Arg381Gln) with CD. The ATG16L1 variant rs2241880 was associated with increased susceptibility to CD (combined OR G ¼ 1.38; 95% confidence interval, 1.29-1.48) and a nondominant mode of inheritance (suggesting that the effect of heterozygosity lies exactly in the middle of extreme homozygotes, h ¼ 0). The IL23R variant rs11209026 was associated with significant protection (OR G ¼ 0.46; 95% confidence interval, 0.41-0.53) and a recessive mode of inheritance, indicating that the effect of a heterozygous genotype would lie close to the wild-type homozygous genotype. In subgroup analysis, the significant effects persisted across Caucasian ancestry studies and pediatric populations but were lacking across studies in Asian populations.Conclusions: The ATG16L1 variant rs2241880 was associated with 38% increase in the risk for CD for higher mutational load, whereas IL23R variant rs11209026 decreased the risk by 54% for higher mutational load. The mode of inheritance for ATG16L1 variant demonstrated perfect additivity for genetic risk, whereas it showed recessiveness for the IL23R variant. This analysis permits risk stratification for CD based on the mutational status and highlight the need for additional studies in certain populations. (Inflamm Bowel Dis 2015;21:768-776)

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Section: Il23r Variant Rs11209026 and Disease Susceptibilitymentioning

confidence: 99%

“…Nine control populations deviated from HWE equilibrium, 42,44,[50][51][52]54,56,57,59 and the combined effects were recalculated after genotype correction with their expected distribution. These effects did not change after correcting for HWE deviations, and they appear in brackets in Table 3.…”

Section: Il23r Variant Rs11209026 and Disease Susceptibilitymentioning

confidence: 99%

ATG16L1 and IL23R Variants and Genetic Susceptibility to Crohnʼs Disease

Grigoras

Ziakas

Jayamani

et al. 2015

Inflammatory Bowel Diseases

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“…One of the most important components of the IL23/IL23R pathway, namely IL23R, has been shown to form a predisposition for both UC and CD (6,9,32). In IBD patients, the IL23 serum levels are increased, while in IL23R knockout mice, the IBD symptoms have been observed to regress (24,28 (18,32,33). This variant is associated with late onset CD and appears to be protective against CD with ileocolonic involvement (33).…”

Section: Discussionmentioning

confidence: 99%

“…It is thought that the IL23/IL23R signal pathway may play a central role in the pathogenesis of IBD. Though there are studies showing that IL23R, JAK2, and STAT3 cause susceptibility to UC and CD in different ethnic groups, the results are not consistent (6,13,(15)(16)(17)(18)(19)(20)(21). The reason for this discrepancy may be that IBD in different ethnic communities may appear through different predominant mechanisms.…”

Section: Introductionmentioning

confidence: 98%

Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene–gene interactions in Crohn’s disease and ulcerative colitis in a Turkish population

Can¹,

Tezel²,

Gürkan³

et al. 2016

Turk J Gastroenterol

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“…For the meta-analysis of R702W, L1007fs and G908R, we included data from 89, 90 and 96 published articles(for R702W, G908 and L1007fs, respectively) with a combined total of 23,703 cases and 22,873 controls, which were published before December 31 st , 2016(D’Addabbo et al 2009; Schoultz et al 2009; Yazdanyar et al 2009; Csöngei et al 2010; Dassopoulos et al 2010; Gazouli et al 2010; Glas et al 2010; Hoffmann et al 2010; Lacher et al 2010; Sventoraityte et al 2010; Yazdanyar et al 2010; Naderi et al 2011; Adeyanju et al 2012; Azzam et al 2012; Hama et al 2012; Kanaan et al 2012; Akyuz et al 2013; Meddour et al 2014; Boukercha et al 2015; Salkic et al 2015), and conducted the analysis in R using the ‘meta’ package. We calculated the odds ratios for the three variants in the meta-analysis using DerSimonian-Laird statistics as a random-effects model.…”

Section: Methodsmentioning

confidence: 99%

Targeted Gene Sequencing in Children with Crohn’s Disease and Their Parents: Implications for Missing Heritability

Chen

Kugathasan

et al. 2018

G3 Genes|Genomes|Genetics

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Crohn’s disease is a complex genetic trait characterized by chronic relapsing intestinal inflammation. Genome wide association studies (GWAS) have identified more than 170 loci associated with the disease, accounting for ∼14% of the disease variance. We hypothesized that rare genetic variation in GWAS positional candidates also contribute to disease pathogenesis. We performed targeted, massively-parallel sequencing of 101 genes in 205 children with Crohn’s disease, including 179 parent-child trios and 200 controls, both of European ancestry. We used the gene burden test implemented in VAAST and estimated effect sizes using logistic regression and meta-analyses. We identified three genes with nominally significant p-values: NOD2, RTKN2, and MGAT3. Only NOD2 was significant after correcting for multiple comparisons. We identified eight novel rare variants in NOD2 that are likely disease-associated. Incorporation of rare variation and compound heterozygosity nominally increased the proportion of variance explained from 0.074 to 0.089. We estimated the population attributable risk and total heritability of variation in NOD2 to be 32.9% and 3.4%, respectively, with 3.7% and 0.25% accounted for by rare putatively functional variants. Sequencing probands (as opposed to genotyping) to identify rare variants and incorporating phase by sequencing parents can recover a portion of the missing heritability of Crohn’s disease.

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NOD2/CARD15 and IL23R genetic variability in 204 Algerian Crohn's disease

Cited by 12 publications

References 32 publications

ATG16L1 and IL23R Variants and Genetic Susceptibility to Crohnʼs Disease

ATG16L1 and IL23R Variants and Genetic Susceptibility to Crohnʼs Disease

Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene–gene interactions in Crohn’s disease and ulcerative colitis in a Turkish population

Targeted Gene Sequencing in Children with Crohn’s Disease and Their Parents: Implications for Missing Heritability

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