Transforming growth factor-β1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study

Kumar, Pradeep; Misra, Shubham; Kumar, Amit; Mohammad, Faruq; Shakya, Sunil; Vardhan, Gyan; Subbiah, Vivekanandhan; Srivastava, Achal Kumar; Prasad, Kameshwar

doi:10.4103/0972-2327.199910

Cited by 10 publications

(3 citation statements)

References 36 publications

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“…This cytokine is elevated in the brain following IS and may exert anti-inflammatory, antiapoptotic and neuroprotective effects, thereby improving repair mechanisms and favoring nerve regeneration [82][83][84]. There are now some publications showing that genetic TGFB1 variants are associated with IS [85]. Moreover, the effects of TGF-β1 on multiple target genes (including ECM) are mediated via the SMAD signaling pathway [86,87], which was significantly enriched in the hemostasis subnetwork list, albeit SMAD/MAD did not make the top five.…”

Section: These Results Indicate That Altered Expression Of These Pathways and Transcriptional Factors May Lead To Death Due To Ismentioning

confidence: 99%

New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses

Maes

Nikiforov

Plaimas

et al. 2021

IJMS

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This study used established biomarkers of death from ischemic stroke (IS) versus stroke survival to perform network, enrichment, and annotation analyses. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of IL6, ALB, TNF, SERPINE1, VWF, VCAM1, TGFB1, and SELE. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches ALB and VWF. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with TLR2/4, TNF, JAK-STAT, NOD, IL10, IL13, IL4, and TGF-β1/SMAD pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due to IS were platelet degranulation and activation, the intrinsic pathway of fibrin clot formation, the urokinase-type plasminogen activator pathway, post-translational protein phosphorylation, integrin cell-surface interactions, and the proteoglycan-integrin extracellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: (a) that NFKB1, RELA and SP1 were the major regulating actors of the PPI network; and (b) hsa-mir-26-5p and hsa-16-5p were the major regulating microRNA actors. In conclusion, prevention of death due to IS should consider that current IS treatments may be improved by targeting VWF, the proteoglycan-integrin-ECM complex, TGF-β1/SMAD, NF-κB/RELA and SP1.

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Section: These Results Indicate That Altered Expression Of These Pathways and Transcriptional Factors May Lead To Death Due To Ismentioning

confidence: 99%

New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses

Maes

Nikiforov

Plaimas

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…This cytokine is elevated in the brain following IS and may exert anti-inflammatory, anti-apoptotic and neuroprotective effects thereby improving repair mechanisms and favoring nerve regeneration [82][83][84]. There are now some publications showing that genetic TGFB1 variants are associated with IS [85]. Moreover, the effects of TGF-β1 on multiple target genes (including ECM) are mediated via the SMAD signaling pathway [86,87], which was significantly enriched in the hemostasis subnetwork list, albeit SMAD/MAD did not make the top-5.…”

Section: The Network and Subnetwork Of Death Due To Strokementioning

confidence: 99%

New Drug Targets to Prevent Death due to Stroke: Results of Protein-Protein Interaction Network, Enrichment and Annotation Analyses.

Maes¹,

Nikiforov²,

Plaimas³

et al. 2021

Preprint

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This study used established biomarkers of death due to ischemic stroke (IS) and performed network, enrichment, and annotation analysis. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of IL6, ALB, TNF, SERPINE1, VWF, VCAM1, TGFB1, and SELE. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches ALB and VWF. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with TLR2/4, TNF, JAK-STAT, NOD, IL10, IL13, IL4, and TGF-β1/SMAD pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due IS were platelet degranulation and activation, the intrinsic pathway of fibrin clot formation, the urokinase-type plasminogen activator pathway, post-translational protein phosphorylation, integrin cell surface interactions, and the proteoglycan-integrin-extra cellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: a) that NFKB1, RELA and SP1 were the major regulating actors of the PPI network; and b) hsa-mir-26-5p and hsa-16-5p were the major regulating microRNA actors. In conclusion, prevention of death due to IS should consider that current IS treatments may be improved by targeting VWF, VEGFA, proteoglycan-integrin-ECM complex, NFKB/RELA and SP1.

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“…190180) is believed to have a crucial role in the induction of ECM production. Several polymorphism loci and single nucleotide polymorphisms (SNPs) have been investigated in the TGF- β 1 gene [ 15 ]. The 869T > C polymorphism is one of the best-known polymorphisms in the TGF- β 1 gene and is known to be associated with several diseases [ 16 – 18 ] and eye disorders [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Glutathione S-Transferase Omega-2 and Transforming Growth Factor-β1 Polymorphisms in Iranian Glaucoma Patients

Bamdad

Sanie-Jahromi

Alamolhoda

et al. 2021

Journal of Ophthalmology

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Background. To investigate the association of glutathione s-transferase omega 2 (GSTO2) (142N > D) and transforming growth factor-β1 (TGF-β1) (869T > C) gene polymorphisms on the pathogenesis of two common types of glaucoma (including primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG)) in the Iranian population. Methods. A total of 100 glaucoma patients (60% males and 40% females with an age mean ± SD of 34.66 ± 14.25 years; 56 cases of POAG and 44 cases of CACG) were enrolled in this study. GSTO2 (142N > D) and TGF-β1 (869T > C) polymorphisms were evaluated by PCR-based methods in patients and controls. Results. At locus GSTO2 (142N > D), the odds of ND genotype with respect to DD and NN genotypes were 1.55 and 2.08 times higher in POAG and CACG patients compared to those of patients in the control group (95% CI1: 0.80–2.98; 95% CI2: 1.00–4.33) which was statistically significant in CACG patients. However, the odds of DD and NN genotypes against the reference genotype in two patients group were not statistically significant as compared to those of patients in the control group. There was a significant association between the ND genotype and male patients (OR = 2.28, 95% CI: 1.06–4.92). The analysis of TGF-β1 (869T > C) polymorphisms showed no significant difference between the genotypes of TGF-β1 (869T > C) polymorphisms in patients and control groups; however, the CT genotype of TGF-β1 significantly differed between female controls and patients (OR = 0.42, 95% CI: 0.18–0.96). Conclusion. The presented results revealed that there was a significant association between the ND genotype of GSTO2 and the pathogenesis of glaucoma. Furthermore, this genotype can be considered as a sex-dependent genetic risk factor for the development of glaucoma. In contrast, the CT genotype of TGF-β1 is suggested to be a protective genetic factor against the pathogenesis of glaucoma.

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Transforming growth factor-β1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study

Cited by 10 publications

References 36 publications

New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses

New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses

New Drug Targets to Prevent Death due to Stroke: Results of Protein-Protein Interaction Network, Enrichment and Annotation Analyses.

Glutathione S-Transferase Omega-2 and Transforming Growth Factor-β1 Polymorphisms in Iranian Glaucoma Patients

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