Association between MDR1 gene polymorphisms and the risk of Crohn’s disease in a cohort of Algerian pediatric patients

Bouzidi, Amira; Mesbah-Amroun, Hamida; Boukercha, Aziza; Benhassine, Fadila; Belboueb, Réda; Berkouk, Karima; Messadi, W.; Touil-Boukoffa, Chafia

doi:10.1038/pr.2016.163

Cited by 7 publications

(3 citation statements)

References 38 publications

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“…40,41 A particular polymorphism within the MDR1 gene, 1236T, has also been associated with an increased risk for prospective surgery in CD patients. 42 The ability of BT-11 to provide therapeutic efficacy in the absence of this gene is an important indication of robustness in the presence of genetic abnormalities and suggest high potential for human translation in a surgery-sparing context. Across all 3 models, BT-11 provides consistent downregulation of Th1 and neutrophil cellular responses and expression of inflammatory cytokines IFNγ, TNFα, MCP1, and IL-6 combined with an increase in Treg populations and IL-10 expression.…”

Section: Discussionmentioning

confidence: 99%

Activation of LANCL2 by BT-11 Ameliorates IBD by Supporting Regulatory T Cell Stability Through Immunometabolic Mechanisms

Leber¹,

Hontecillas²,

Zoccoli-Rodriguez³

et al. 2018

Inflammatory Bowel Diseases

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Section: Discussionmentioning

confidence: 99%

Activation of LANCL2 by BT-11 Ameliorates IBD by Supporting Regulatory T Cell Stability Through Immunometabolic Mechanisms

Leber¹,

Hontecillas²,

Zoccoli-Rodriguez³

et al. 2018

Inflammatory Bowel Diseases

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“…The multi-drug resistance gene MDR1 single nucleotide polymorphisms (SNPs) C1236T and G2577A/T have also been shown to be associated with CD in an Algerian pediatric CD population[6]. …”

Section: Introductionmentioning

confidence: 99%

Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

Lin

Wang

Hegarty

et al. 2017

WJG

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AIMTo study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD).METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs.RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287).CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.

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“…Accumulating evidence had shows that genes [10] and signaling pathways [11] mainly contribute to the occurrence and advancement of CD. Genes include MDR1 [12], ACE2 [13], NUDT15 [14], HNF4A [15] and IL23R [16] are responsible for progression of CD. Signaling pathways include JAK/STAT signaling pathway [17], STING signaling pathway [18], TLRs and dectin-1 signaling pathways [19], NF□κB and MAPK signaling pathways [20] and P2X7R-Pannexin-1 signaling pathway [21] are involved in advancement of CD.…”

Section: Introductionmentioning

confidence: 99%

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Pediatric Crohn's Disease (CD) also known as inflammatory bowel diseases, affects millions of people all over the world. The aim of this investigation is to identify the key genes in CD and uncover their potential functions. We downloaded the next generation sequencing (NGS) dataset GSE73374 from the Gene Expression Omnibus (GEO) database. The NGS dataset GSE73374 was used to screen differentially expressed genes (DEGs) between samples from patients with CD and healthy controls. Gene ontology (GO) and REACTOME pathway enrichment analyses were applied for the DEGs. Subsequently, a protein - protein interaction (PPI) network, modules, miRNA- hub gene regulatory network and TF - hub gene regulatory network were constructed to identify hub genes, miRNAs and TFs. Receiver operating characteristic curve (ROC) analysis was applied to validate the hub genes. A total of 957 DEGs were identified, including 478 up regulated genes and 479 down regulated genes. GO and REACTOME results suggested that several Go terms and pathways are involved in response to stimulus, extracellular region, signaling receptor binding, small molecule metabolic process, membrane, transporter activity, immune system and biological oxidations. The top centrality hub genes MDFI, MNDA, FBXO6, TFRC, STAT1, DPP4, MME, SLC39A4, APOA1 and TMEM25 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation identified key genes and signal pathways, which might help us improve our understanding of the molecular mechanisms of CD and identify some novel therapeutic targets for CD.

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Association between MDR1 gene polymorphisms and the risk of Crohn’s disease in a cohort of Algerian pediatric patients

Cited by 7 publications

References 38 publications

Activation of LANCL2 by BT-11 Ameliorates IBD by Supporting Regulatory T Cell Stability Through Immunometabolic Mechanisms

Activation of LANCL2 by BT-11 Ameliorates IBD by Supporting Regulatory T Cell Stability Through Immunometabolic Mechanisms

Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

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