Genetic susceptibility to DFUs remains underrecognized despite the high clinical burden in India. A study published in the Journal of Diabetes & Metabolic Disorders synthesized evidence on genetic polymorphisms associated with DFU risk in Indian populations.
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, the review screened PubMed, ScienceDirect, and Google Scholar databases up to July 2025. Nineteen genetic comparisons from case–control studies were included. Meta-analysis was conducted using standard statistical software for systematic reviews (version 5.4.1), with subgroup evaluations across inflammation, angiogenesis, immune regulation, and extracellular matrix (ECM) remodeling pathways.
Pooled results demonstrated a significantly higher DFU risk among carriers of susceptibility alleles (odds ratio [OR] 2.76; 95% confidence interval [CI] 1.93–3.94; p<0.00001). Angiogenesis-related variants showed the strongest associations, including HIF-1α (OR 4.97) and VEGF (OR 5.60), emphasizing the central role of vascular dysfunction. Oxidative stress–related genes exhibited exceptionally high effect sizes, particularly HSP70 C243T_2 (OR 19.45) and Nrf2 polymorphisms. Immune pathway variants, such as toll-like receptor 4 (TLR4), showed moderate associations, while ECM-related genes demonstrated smaller but statistically significant effects.
These findings identify diabetic foot ulcer susceptibility as a multifactorial genetic phenotype shaped by angiogenic, inflammatory, oxidative, immune, and structural pathways. Incorporating genetic markers into risk assessment may enhance prediction models and support targeted prevention strategies for high-risk diabetic populations in India.
