Influence of IL-6, IL-10, IFN-γ and TNF-α genetic variants on susceptibility to diabetic kidney disease in type 2 diabetes mellitus patients

Fathy, Shadia A.; Mohamed, Mohamed R.; Ali, Mohamed A.; EL-Helaly, Ashraf E.; Alattar, Abdulnabi

doi:10.1080/1354750x.2018.1501761

Cited by 65 publications

(42 citation statements)

References 47 publications

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“…For example, cytokine-mediated signaling pathway, apoptosis signaling pathway, reactive oxygen species metabolic process, regulation of in ammatory response, etc. Relevant studies have shown that the occurrence and development of DN is related to cell dysfunction and damage [ 40 , 41 ], chronic in ammatory in ltration [ 42 ], cell apoptosis, and oxidative stress [ 43 ]. This indicates that the main target genes are important for multiple BP.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanisms Underlying the Therapeutic Effect of Salvia Miltiorrhiza Against Diabetic Nephropathy Using Network Pharmacology and Molecular Docking

Zhang

Han

Wang

et al. 2020

Preprint

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BackgroundThe mechanisms underlying the therapeutic effect of Salvia Miltiorrhiza (SM) against diabetic nephropathy (DN) using systematic network pharmacology and molecular docking methods were examined.MethodsTCMSP database was used to screen the active ingredients of SM. Gene targets were obtained using Swiss Target Prediction and TCMSP databases. Related targets of DN were retrieved from the Genecards and DisGeNET databases. Next, a PPI network was constructed using the common targets of SM-DN in the STRING database. The Metascape platform was used for GO function analysis and Cytoscape plug-in ClueGO was used for KEGG pathway enrichment analysis. Molecular docking was performed using iGEMDOCK and AutoDock Vina software. Pymol and LigPlos were used for mapping the network. ResultsSixty-six active ingredients and 189 targets were screened from SM. Among them, 64 targets overlapped with DN targets. The PPI network diagram revealed that AKT1, VEGFA, IL6, TNF, MAPK1, TP53, EGFR, STAT3, MAPK14, and JUN were the top 10 relevant targets. GO and KEGG analyses mainly focused on advanced glycation end products, oxidative stress, inflammatory response, and immune regulation. Molecular docking revealed that the potential target genes closely related to DN, including TNF, NOS2, and AKT1, were more stable in combination with salvianolic acid B, and their stability was better than that of tanshinone IIA.ConclusionThis study reveals the active components and potential molecular mechanisms involved in the therapeutic effect of SM against DN and provides a reference for the wide application of SM in clinically managing DN.

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Section: Discussionmentioning

confidence: 99%

Exploring the Mechanisms Underlying the Therapeutic Effect of Salvia Miltiorrhiza Against Diabetic Nephropathy Using Network Pharmacology and Molecular Docking

Zhang

Han

Wang

et al. 2020

Preprint

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“…1). Ultimately, 14 eligible articles (including 19 independent studies) were selected for the present meta-analysis [12,[21][22][23][24][25][26][27][28][29][30][31][32][33]. Among these, 11 studies exist with outcomes for DN and 8 studies with outcomes for DR to incorporate into this meta-analysis.…”

Section: Characteristics Of the Studies Includedmentioning

confidence: 99%

Effects of TNF-α-308G/A Polymorphism on the Risk of Diabetic Nephropathy and Diabetic Retinopathy: An Updated Meta-Analysis

et al. 2020

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Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the major factors of morbidity and mortality in the patients with diabetes mellitus (DM). Growing studies have investigated the relationship between the TNF-α-308G/A polymorphism and the susceptibility to DN and DR, without achieving consensus. Thus, we conducted this meta-analysis to reach more comprehensive conclusions for these issues. Eligible studies were retrieved through electronic databases such as PubMed, Embase, Web of Science and China National Knowledge Infrastructure. Summary of odds ratios (OR) and 95% confidence intervals (CIs) were generated to evaluate the intensity of the associations. Statistical analyses were performed by STATA 11.0 and RevMan 5.2. There are fourteen eligible publications involving nineteen studies in this meta-analysis. TNF-α-308G/A polymorphism was significantly related to increasing risk of DN under recessive model (OR=1.37, 95% CI=1.03–1.83) and homozygous model (OR=1.54, 95% CI=1.15–2.06). Moreover, the similar results were also obtained in Asian groups for DN (recessive: OR=1.69, 95% CI=1.18–2.42; homozygous: OR=1.99, 95% CI=1.38–2.86; respectively), and significant association was also detected between TNF-α-308G/A and DN susceptibility in type 2 DM in recessive model (OR=1.39, 95% CI=1.02–1.89). No significant association was observed between TNF-α-308G/A and DR susceptibility in total analyses and subgroup analyses by ethnicity and type of DM. TNF-α-308G/A polymorphism may enhance the susceptibility to diabetic nephropathy, especially in Asian population and in T2DM patients, but not diabetic retinopathy.

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“…Our results were consistent with most other studies. The study of Rudofsky et al [19] did not find any association between IL-6 -174G/C polymorphism and diabetic neuropathy or diabetic nephropathy in T2DM, which was supported by some other studies [16,17,20]. The study of Paine et al [9] indicated that the promoter polymorphism of IL-6 was not a potent risk factor for the pathogenesis of proliferative diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 81%

“…Studies have confirmed that IL-6 and its expression are associated with insulin resistance and β-cell dysfunction, diabetic retinopathy and obstructive sleep apnea hypopnea syndrome (OSAHS) in T2DM [13][14][15]. However, IL-6 level in T2DM patients with diabetic microvascular complications is considered to be no higher than in patients without complications [16,17]. SNP rs1800795 (-174G/C) of IL-6 gene in T2DM was first reported in 2003 showing that GG phenotype was a genetic determination of inflammation in the development of T2DM [18].…”

Section: Discussionmentioning

confidence: 99%

The association of interieukin-6 polymorphism (rs1800795) with microvascular complications in Type 2 diabetes mellitus

et al. 2020

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Objectives: To evaluate the effects of the single-nucleotide polymorphism (SNP) rs1800795 in interieukin-6 (IL-6) gene on diabetic microvascular complications of Type 2 diabetes mellitus (T2DM), using statistical meta-analysis. Methods: Literature pertaining to the relationship between the SNP rs1800795 and microvascular complications of T2DM including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and foot disease was retrieved from PubMed, Web of Science Knowledge and SinoMed databases. Original information was analyzed using Stata 12.0, including meta-analysis statistics, test for heterogeneity, evaluation of publication bias and sensitivity. Subgroup analysis was conducted to assess the effect of specific factors on the corresponding results. Results: In total, 14 eligible articles were obtained. The SNP rs1800795 in IL-6 gene is not correlated with risk of microvascular complications in T2DM. Among the original literature, a genetic model (OR = 1.071, 95% CI: 0.681–1.685, P=0.767), an allelic genetic model (OR = 1.010, 95% CI: 0.959–1.063, P=0.703), a heterozygote genetic model (OR = 1.107, 95% CI: 0.916–1.339, P=0.292), a dominant genetic model (OR = 1.108, 95% CI: 0.885–1.387, P=0.372), and a recessive genetic model (OR = 0.978, 95% CI: 0.646–1.478, P=0.917) were included respectively. In the subgroup analysis by types of diabetic microvascular complications, we found no correlation between the SNP rs1000795 polymorphism and complications of T2DM in either the homozygote genetic model or the allelic genetic model (P<0.05). Conclusion: Our results demonstrate that rs1800795 polymorphism in IL-6 gene is not correlated with the susceptibility of microvascular complications of T2DM.

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Influence of IL-6, IL-10, IFN-γ and TNF-α genetic variants on susceptibility to diabetic kidney disease in type 2 diabetes mellitus patients

Cited by 65 publications

References 47 publications

Exploring the Mechanisms Underlying the Therapeutic Effect of Salvia Miltiorrhiza Against Diabetic Nephropathy Using Network Pharmacology and Molecular Docking

Exploring the Mechanisms Underlying the Therapeutic Effect of Salvia Miltiorrhiza Against Diabetic Nephropathy Using Network Pharmacology and Molecular Docking

Effects of TNF-α-308G/A Polymorphism on the Risk of Diabetic Nephropathy and Diabetic Retinopathy: An Updated Meta-Analysis

The association of interieukin-6 polymorphism (rs1800795) with microvascular complications in Type 2 diabetes mellitus

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