In Silico Characterization of Inflammatory and Anti-Inflammatory Modulation in Diabetic Nephropathy: The Construction of a Genetic Panel

Diabetic Nephropathy (DN) stands as a primary cause of end-stage renal disease and its etiology remains unclear. Thus, this study aims to construct a genetic panel with potential biomarkers linked to the inflammatory pathway of DN associated with the pathology’s susceptibility. Through a systematic...

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Published in:	Journal of Molecular Pathology Vol. 5; no. 3; pp. 335 - 359
Main Authors:	Costa, Caroline Christine Pincela da, Assunção, Leandro do Prado, Santos, Kamilla de Faria, Silva, Laura da, Santos, Rodrigo da Silva, Reis, Angela Adamski da Silva
Format:	Journal Article
Language:	English
Published:	Basel MDPI AG 01-09-2024
Subjects:	Bias Bioinformatics Chemokines Cohort analysis Confounding (Statistics) Content analysis Cross-sectional studies Datasets Diabetes Diabetes mellitus Diabetic nephropathy End-stage renal disease Etiology Gene expression Genetic analysis genetic polymorphisms Hyperglycemia inflammation Kidney diseases Kidneys Leukocytes Meta-analysis microvascular complications Monocyte chemoattractant protein 1 Nephropathy Polymorphism Precision medicine Protein arrays Proteins Public health Single-nucleotide polymorphism Software susceptibility Systematic review Vascular endothelial growth factor
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Abstract	Diabetic Nephropathy (DN) stands as a primary cause of end-stage renal disease and its etiology remains unclear. Thus, this study aims to construct a genetic panel with potential biomarkers linked to the inflammatory pathway of DN associated with the pathology’s susceptibility. Through a systematic review and meta-analysis, we selected observational studies in English, Portuguese, and Spanish, selected from the PubMed, SCOPUS, Virtual Health Library, Web of Science, and EMBASE databases. Additionally, a protein–protein interaction network was constructed to list hub genes, with differential expression analysis by microarray of kidneys with DN from the GSE30529 database to further refine results. Seventy-two articles were included, and 54 polymorphisms in 37 genes were associated with the inflammatory pathway of DN. Meta-analysis indicated a higher risk of complication associated with SNPs 59029 G/A, −511 C/T, VNTR 86 bp, −308 G/A, and −1031 T/C. Bioinformatics analyses identified differentially expressed hub genes, underscoring the scarcity of studies on CCL2 and VEGF-A genes in relation to DN. This study highlighted the intrinsic relationship between inflammatory activity in the etiology and progression of DN, enabling the effective application of precision medicine in diabetic patients for potential prognosis of the complications and contributing to cost reduction in the public health system.
AbstractList	Diabetic Nephropathy (DN) stands as a primary cause of end-stage renal disease and its etiology remains unclear. Thus, this study aims to construct a genetic panel with potential biomarkers linked to the inflammatory pathway of DN associated with the pathology’s susceptibility. Through a systematic review and meta-analysis, we selected observational studies in English, Portuguese, and Spanish, selected from the PubMed, SCOPUS, Virtual Health Library, Web of Science, and EMBASE databases. Additionally, a protein–protein interaction network was constructed to list hub genes, with differential expression analysis by microarray of kidneys with DN from the GSE30529 database to further refine results. Seventy-two articles were included, and 54 polymorphisms in 37 genes were associated with the inflammatory pathway of DN. Meta-analysis indicated a higher risk of complication associated with SNPs 59029 G/A, −511 C/T, VNTR 86 bp, −308 G/A, and −1031 T/C. Bioinformatics analyses identified differentially expressed hub genes, underscoring the scarcity of studies on CCL2 and VEGF-A genes in relation to DN. This study highlighted the intrinsic relationship between inflammatory activity in the etiology and progression of DN, enabling the effective application of precision medicine in diabetic patients for potential prognosis of the complications and contributing to cost reduction in the public health system.
Author	Santos, Rodrigo da Silva Santos, Kamilla de Faria Silva, Laura da Costa, Caroline Christine Pincela da Reis, Angela Adamski da Silva Assunção, Leandro do Prado
Author_xml	– sequence: 1 givenname: Caroline Christine Pincela da surname: Costa fullname: Costa, Caroline Christine Pincela da – sequence: 2 givenname: Leandro do Prado surname: Assunção fullname: Assunção, Leandro do Prado – sequence: 3 givenname: Kamilla de Faria surname: Santos fullname: Santos, Kamilla de Faria – sequence: 4 givenname: Laura da surname: Silva fullname: Silva, Laura da – sequence: 5 givenname: Rodrigo da Silva orcidid: 0000-0002-9480-4362 surname: Santos fullname: Santos, Rodrigo da Silva – sequence: 6 givenname: Angela Adamski da Silva orcidid: 0000-0002-8281-7334 surname: Reis fullname: Reis, Angela Adamski da Silva
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Snippet	Diabetic Nephropathy (DN) stands as a primary cause of end-stage renal disease and its etiology remains unclear. Thus, this study aims to construct a genetic...
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SubjectTerms	Bias Bioinformatics Chemokines Cohort analysis Confounding (Statistics) Content analysis Cross-sectional studies Datasets Diabetes Diabetes mellitus Diabetic nephropathy End-stage renal disease Etiology Gene expression Genetic analysis genetic polymorphisms Hyperglycemia inflammation Kidney diseases Kidneys Leukocytes Meta-analysis microvascular complications Monocyte chemoattractant protein 1 Nephropathy Polymorphism Precision medicine Protein arrays Proteins Public health Single-nucleotide polymorphism Software susceptibility Systematic review Vascular endothelial growth factor
Title	In Silico Characterization of Inflammatory and Anti-Inflammatory Modulation in Diabetic Nephropathy: The Construction of a Genetic Panel
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