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

Senhaji, Nezha; Nadifi, Sellama; Zaid, Younes; Serrano, Aurelio; Rodríguez, Daniel Salazar; Serbati, Nadia; Karkouri, Mehdi; Badre, Wafaa; Martı́n, Javier

doi:10.3748/wjg.v23.i47.8300

Cited by 10 publications

(10 citation statements)

References 36 publications

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“…NOS2 encodes the synthesis of inducible nitric oxide synthase (iNOS). The highly expressed iNOS in the inflamed mucosa plays a key role in oxidative stress-induced inflammation [ 23 ]. NOS activity in colon biopsies has been shown to be correlated with disease intensity [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Based on Network Pharmacology to Explore the Molecular Targets and Mechanisms of Gegen Qinlian Decoction for the Treatment of Ulcerative Colitis

Wei

et al. 2020

BioMed Research International

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Background. Gegen Qinlian (GGQL) decoction is a common Chinese herbal compound for the treatment of ulcerative colitis (UC). In this study, we aimed to identify its molecular target and the mechanism involved in UC treatment by network pharmacology and molecular docking. Material and Methods. The active ingredients of Puerariae, Scutellariae, Coptis, and Glycyrrhiza were screened using the TCMSP platform with drug ‐ like properties DL ≥ 0.18 and oral availability OB ≥ 30 % . To find the intersection genes and construct the TCM compound-disease regulatory network, the molecular targets were determined in the UniProt database and then compared with the UC disease differential genes with P value < 0.005 and ∣ log 2 fold change ∣ > 1 obtained in the GEO database. The intersection genes were subjected to protein-protein interaction (PPI) construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After screening the key active ingredients and target genes, the AutoDock software was used for molecular docking, and the best binding target was selected for molecular docking to verify the binding activity. Results. A total of 146 active compounds were screened, and quercetin, kaempferol, wogonin, and stigmasterol were identified as the active ingredients with the highest associated targets, and NOS2, PPARG, and MMP1 were the targets associated with the maximum number of active ingredients. Through topological analysis, 32 strongly associated proteins were found, of which EGFR, PPARG, ESR1, HSP90AA1, MYC, HSPA5, AR, AKT1, and RELA were predicted targets of the traditional Chinese medicine, and PPARG was also an intersection gene. It was speculated that these targets were the key to the use of GGQL in UC treatment. GO enrichment results showed significant enrichment of biological processes, such as oxygen levels, leukocyte migration, collagen metabolic processes, and nutritional coping. KEGG enrichment showed that genes were particularly enriched in the IL-17 signaling pathway, AGE-RAGE signaling pathway, toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, transcriptional deregulation in cancer, and other pathways. Molecular docking results showed that key components in GGQL had good potential to bind to the target genes MMP3, IL1B, NOS2, HMOX1, PPARG, and PLAU. Conclusion. GGQL may play a role in the treatment of ulcerative colitis by anti-inflammation, antioxidation, and inhibition of cancer gene transcription.

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Section: Discussionmentioning

confidence: 99%

Based on Network Pharmacology to Explore the Molecular Targets and Mechanisms of Gegen Qinlian Decoction for the Treatment of Ulcerative Colitis

Wei

et al. 2020

BioMed Research International

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“…Genetic variants within the NOS2 gene have been associated with IBD susceptibility in different populations (Martín et al, 2007;Senhaji et al, 2017), and increased mRNA levels were found in the colonic mucosa of patients with active UC, compared to patients with inactive UC and controls, and in CD patients compared to controls (Coburn et al, 2016). Recently, Luther and collaborators found that colonic expression of NOS2 was elevated in patients with loss of response to TNFα-antagonist compared to responders (Luther et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Mucosal gene expression changes induced by anti‐TNF treatment in inflammatory bowel disease patients

Milanesi

Dobre

Manuc

et al. 2019

Drug Development Research

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In the last two decades anti‐tumor necrosis factor (anti‐TNF) therapy for inflammatory bowel disease (IBD) has been widely used to induce and maintain clinical and endoscopical remission, completely changing management of the disease. In this study, we aimed to identify gene expression changes in inflamed mucosa from Crohn's disease and ulcerative colitis patients treated with 5‐aminosalicylic acid (5‐ASA) (N = 25) or anti‐TNF agents (N = 12) compared to drug‐free IBD patients (N = 12) and non‐IBD control subjects (N = 18). The mucosal expression of 84 genes previously associated with IBD was evaluated by qPCR. We found that both therapeutic regimens induce a decrease in LCN2, NOS2, and TFF1, the levels of which are overexpressed in drug‐free patients compared to non‐IBD control subjects. Interestingly, a stronger effect of anti‐TNF drugs was observed on LCN2 and TFF1 levels. However, 5‐ASA seems to induce a more robust reduction of NOS2 expression. Moreover, we found that anti‐TNF treatment significantly increased ABCB1, leading to levels similar to those found in non‐IBD control subjects.

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“…The association of diabetic complication risk was also supported by a previous meta-analysis report [ 75 ]. Also the subgroup analysis results of HIF1A 1772 C/T polymorphism showed insignificant association with autoimmune diseases, inflammatory diseases, and preeclampsia under all five genetic models which goes in favor of Wipff et al [ 31 ] and Feng et al [ 25 ] for autoimmune disease, Torres et al [ 27 ], Chachami et al [ 32 ] and Senhaji et al [ 41 ] for inflammatory disease, and Nava-Salazar et al [ 34 ] for preeclampsia. The subgroup analysis results of HIF1A 1790 G/A polymorphism showed significant association with CVD under homozygote model ( AA vs. GG ) and diabetic complications under allelic ( A vs. G ) and homozygote ( AA vs. GG ) models.…”

Section: Discussionmentioning

confidence: 96%

“…Similarly, some authors showed the significant association of HIF1A (1772 C/T and 1790 G/A) with cardiovascular diseases (CVD) [ 21 , 40 ], though some authors did not find the significant effect in the same question [ 22 , 26 ]. Again for inflammatory diseases, a significant association was claimed by [ 20 , 38 ], and an insignificant association by [ 27 , 32 , 41 ]. For Chronic obstructive pulmonary disease (COPD), Yu et al [ 17 ] and Putra et al [ 39 ] claimed the significant and insignificant association with HIF1A gene polymorphisms, respectively.…”

Section: Introductionmentioning

confidence: 99%

Association of hypoxia inducible factor 1-Alpha gene polymorphisms with multiple disease risks: A comprehensive meta-analysis

et al. 2022

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HIF1A gene polymorphisms have been confirmed the association with cancer risk through the statistical meta-analysis based on single genetic association (SGA) studies. A good number SGA studies also investigated the association of HIF1A gene with several other diseases, but no researcher yet performed statistical meta-analysis to confirm this association more accurately. Therefore, in this paper, we performed a statistical meta-analysis to draw a consensus decision about the association of HIF1A gene polymorphisms with several diseases except cancers giving the weight on large sample size. This meta-analysis was performed based on 41 SGA study’s findings, where the polymorphisms rs11549465 (1772 C/T) and rs11549467 (1790 G/A) of HIF1A gene were analyzed based on 11544 and 7426 cases and 11494 and 7063 control samples, respectively. Our results showed that the 1772 C/T polymorphism is not significantly associated with overall disease risks. The 1790 G/A polymorphism was significantly associated with overall diseases under recessive model (AA vs. AG + GG), which indicates that the A allele is responsible for overall diseases though it is recessive. The subgroup analysis based on ethnicity showed the significant association of 1772 C/T polymorphism with overall disease for Caucasian population under the all genetic models, which indicates that the C allele controls overall diseases. The ethnicity subgroup showed the significant association of 1790 G/A polymorphism with overall disease for Asian population under the recessive model (AA vs. AG + GG), which indicates that the A allele is responsible for overall diseases. The subgroup analysis based on disease types showed that 1772 C/T is significantly associated with chronic obstructive pulmonary disease (COPD) under two genetic models (C vs. T and CC vs. CT + TT), skin disease under two genetic models (CC vs. TT and CC + CT vs. TT), and diabetic complications under three genetic models (C vs. T, CT vs. TT and CC + CT vs. TT), where C allele is high risk factor for skin disease and diabetic complications (since, ORs > 1), but low risk factor for COPD (since, ORs < 1). Also the 1790 G/A variant significantly associated with the subgroup of cardiovascular disease (CVD) under homozygote model, diabetic complications under allelic and homozygote models, and other disease under four genetic models, where the A is high risk factor for diabetic complications and low risk factor for CVD. Thus, this study provided more evidence that the HIF1A gene is significantly associated with COPD, CVD, skin disease and diabetic complications. These might be the severe comorbidities and risk factors for multiple cancers due to the effect of HIF1A gene and need further investigations accumulating large number of studies.

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

Cited by 10 publications

References 36 publications

Based on Network Pharmacology to Explore the Molecular Targets and Mechanisms of Gegen Qinlian Decoction for the Treatment of Ulcerative Colitis

Based on Network Pharmacology to Explore the Molecular Targets and Mechanisms of Gegen Qinlian Decoction for the Treatment of Ulcerative Colitis

Mucosal gene expression changes induced by anti‐TNF treatment in inflammatory bowel disease patients

Association of hypoxia inducible factor 1-Alpha gene polymorphisms with multiple disease risks: A comprehensive meta-analysis

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