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

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.

Keywords

• diabetes
• microvascular complications
• inflammation
• genetic polymorphisms
• susceptibility