Association of inflammatory cytokine gene polymorphisms with inflammatory bowel disease in a Moroccan cohort

Senhaji, Nezha; Serrano, Aurelio; Badre, Wafaa; Serbati, Nadia; Karkouri, Mehdi; Zaid, Younes; Nadifi, Sellama; Martín, Javier

doi:10.1038/gene.2015.52

Cited by 25 publications

(15 citation statements)

References 36 publications

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“…IL-6 sRa, encoded by the IL6R gene, is significantly controlled by cis-pSNPs (p = 3.57E-11, Table 2 and S5 Table ). GWAS’s have related IL6R to immune diseases and associated traits, including coronary heart disease [ 25 ], pulmonary function [ 26 ], asthma [ 27 ], C-reactive protein [ 27 , 28 ], rheumatoid arthritis [ 29 ] and IBD susceptibility [ 30 , 31 ]. The association of IL6R locus with CAD was genome significant reported Cardiogram study [ 32 ] ( S5 Table ).…”

Section: Resultsmentioning

confidence: 99%

High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors

et al. 2017

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To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of 1128 proteins in IBD patients of European descent (84 Crohn’s Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients). We discovered new, previously unreported aging-associated proteomic traits (such as serum Albumin level), confirmed previously reported results from different tissues (i.e., upregulation of APOE with aging), and found loss of regulation of MMP7 in CD patients. In carrying out a genome wide genotype-protein association study (proteomic Quantitative Trait Loci, pQTL) within the CD patients, we identified 41 distinct proteomic traits influenced by cis pQTLs (underlying SNPs are referred to as pSNPs). Significant overlaps between pQTLs and cis eQTLs corresponding to the same gene were observed and in some cases the QTL were related to inflammatory disease susceptibility. Importantly, we discovered that serum protein levels of MST1 (Macrophage Stimulating 1) were regulated by SNP rs3197999 (p = 5.96E-10, FDR<5%), an accepted GWAS locus for IBD. Filling the knowledge gap of molecular mechanisms between GWAS hits and disease susceptibility requires systematically dissecting the impact of the locus at the cell, mRNA expression, and protein levels. The technology and analysis tools that are now available for large-scale molecular studies can elucidate how alterations in the proteome driven by genetic polymorphisms cause or provide protection against disease. Herein, we demonstrated this directly by integrating proteomic and pQTLs with existing GWAS, mRNA expression, and eQTL datasets to provide insights into the biological processes underlying IBD and pinpoint causal genetic variants along with their downstream molecular consequences.

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Section: Resultsmentioning

confidence: 99%

High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors

et al. 2017

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“…In this line, deregulated TNF signaling is often associated with disease progression in IBD patients [41]. Furthermore, polymorphisms in TNFR1 and TNFR2 have been identiଏed in patients with CD and UC [163][164][165][166] and TNFR2 is frequently upregulated in LP lymphocytes from patients with CD [167].…”

Section: Tnf In Intestinal Inଏammatory Disordersmentioning

confidence: 99%

The many faces of tumor necrosis factor signaling in the intestinal epithelium

Delgado

Brunner

2019

Genes Immun

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The intestinal epithelium represents an exquisite complex combination of specialized cellular components, structural organization, as well as ଏne-tuned maintenance and renewal mechanisms that ensure its barrier and absorptive function. Defects in one or more of these components can lead to devastating consequences for the organisms, and when chronic, even develop into inଏammatory diseases, such as Crohn's disease or ulcerative colitis. In these scenarios, the cytokine TNF (Tumor Necrosis Factor α) appears to be a major inଏammation-promoting and tissue damage-promoting effector molecule. Besides its role in inଏammation and cell death, TNF presents a wide range of pleiotropic activities with implications in various cellular processes, including proliferation and differentiation. Moreover, more recent evidences suggest an anti-inଏammatory role of TNF, mostly via the induction of local glucocorticoids synthesis in the intestinal epithelium. Thus, the outcome of TNF receptor signaling largely depends on various factors, like the TNFR composition and the precise cellular context or tissue type, which will determine the cellular fate. In this review, we discuss the molecular mechanisms and their potential crosstalk that regulate the different TNF-initiated cellular outcomes in the intestine, as well as possible applications for pharmacological interventions in the treatment of inଏammatory disorders of the intestinal mucosa. Highlights • TNF stimulation leads to survival, inଏammation, apoptosis and necroptosis induction, depending on the cellular background and the disruption of speciଏc checkpoints.

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“…The success rates of genotyping assays ranged between 95% and 100%. Baseline demographic and clinical characteristics of cases were reported in a previous paper[ 23 ] and are presented in Table 1 . Differences in our cohort between CD and UC patients in terms of age at diagnosis and gender distribution are to be underlined.…”

Section: Resultsmentioning

confidence: 99%

Polymorphisms in oxidative pathway related genes and susceptibility to inflammatory bowel disease

Senhaji

Nadifi

Zaid

et al. 2017

WJG

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AIMTo investigate whether common variants in the oxidative pathway genes influence inflammatory bowel disease (IBD) risk among Moroccan patients.METHODSThe distribution of (TAAA)n_rs12720460 and (CCTTT)n _rs3833912 NOS2A microsatellite repeats, HIF-1A_rs11549467 and NFKB1-94ins/delATTG_rs28362491 was analyzed in 507 subjects grouped in 199 IBD and 308 healthy controls. Genotyping was performed with polymerase chain reaction-fluorescent method and the TaqMan® allelic discrimination technology.RESULTSThe allele and genotype frequencies of HIF1A_ rs11549467, NFKB1_rs28362491 and NOS2A_ (TAAA)n did not differ significantly between patients and controls. Analysis of NOS2A_ (CCTTT)n markers evidenced differences between patients and healthy controls. A preferential presence of the (CCTTT)8 (P = 0.02; OR = 1.71, 95%CI: 1.07-2.74), (CCTTT)14 (P = 0.02; OR = 1.71, 95%CI: 1.06-2.76) alleles in IBD, (CCTTT)8 (P = 0.008; OR = 1.95, 95%CI: 1.17-3.23) in CD and (CCTTT)7 (P = 0.009; OR = 7.61, 95%CI: 1.25-46.08), (CCTTT)11 (P = 0.05; OR = 0.51, 95%CI: 0.25-1.01), (CCTTT)14 (P = 0.02; OR = 2.05, 95%CI: 1.07-3.94), (CCTTT)15 (P = 0.01; OR = 2.25, 95%CI: 1.16-4.35) repeats in UC patients indicated its possible association with higher disease risk which need to be confirmed in a larger sample size.CONCLUSIONOur results suggest that the NOS2A_ (CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population.

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Association of inflammatory cytokine gene polymorphisms with inflammatory bowel disease in a Moroccan cohort

Cited by 25 publications

References 36 publications

High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors

High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors

The many faces of tumor necrosis factor signaling in the intestinal epithelium

Polymorphisms in oxidative pathway related genes and susceptibility to inflammatory bowel disease

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