Genetic Polymorphism of the Nrf2 Promoter Region (rs35652124) Is Associated with the Risk of Diabetic Foot Ulcers

• Published in: Oxidative medicine and cellular longevity Vol. 2020; no. 2020; pp. 1 - 9
• Main Authors: Rajesh, Kesavan, Ali, Daoud, Dhamodharan, Umapathy, Teena, Rajan, Ramkumar, Kunka Mohanram
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2020; Hindawi; John Wiley & Sons, Inc
• Subjects: Base Sequence; Binding sites; Biomarkers - metabolism; Cholesterol; Clinical Study; Cytokines; Cytokines - genetics; Cytokines - metabolism; Deoxyribonucleic acid; Diabetes; Diabetes Mellitus, Type 2 - genetics; Diabetic foot; Diabetic Foot - genetics; DNA; DNA methylation; DNA sequencing; Enzymes; Epigenetics; Female; Foot diseases; Gene expression; Gene Expression Regulation; Gene Frequency - genetics; Genes; Genetic aspects; Genetic Association Studies; Genetic markers; Genetic Predisposition to Disease; Genetic research; Genetic transcription; Genotype & phenotype; Glucose; Humans; Infectious diseases; Inflammation Mediators - metabolism; Insulin resistance; Leg ulcers; Male; Middle Aged; NF-E2-Related Factor 2 - genetics; Nucleotide sequencing; Oxidative stress; Polymorphism; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic; Single nucleotide polymorphisms; Statistical analysis; Transcription, Genetic; Tumor necrosis factor-TNF; Type 2 diabetes; United States > US
• ISSN: 1942-0900; 1942-0994; 1942-0994
• DOI: 10.1155/2020/9825028

The genetic polymorphism in the nuclear factor erythroid 2-related factor 2 (Nrf2) gene has been reported as one of the prognosis markers for various diseases, including cancer. Nrf2 is a key transcription factor involved in wound healing by regulating angiogenesis. We investigated the genetic association of NRF2 single-nucleotide polymorphism rs35652124 with T2DM and DFU and assessed its functional impact. A total of 400 subjects were recruited for the study and categorized into three groups: infected DFU patients (DFU, n=100), T2DM patients without complications (T2DM, n=150), and healthy adults with normal glucose tolerance (NGT, n=150). The subjects were genotyped by PCR-RFLP, and the polymorphism was identified by bidirectional Sanger sequencing. The expression of NRF2, IL-10, TNF-α, and IL-6 was studied by qPCR to evaluate the functional impact of rs35652124. The “TT” genotype of rs35652124 was associated with a significant risk for T2DM [OR=2.2 (1.2-4.2), p=0.01] and DFU [OR=7.9 (4-14.9), p<0.0001]. A significant decrease in transcriptional levels of NRF2 and IL-10 and a remarkable increase in TNF-α and IL-6 were observed in subjects with TT genotype. In conclusion, rs35652124 (TT) is a harmful genetic variant that predisposes to insulin resistance and impaired angiogenesis. Hence, it may serve as a diagnostic genetic marker for T2DM and DFU in combination with different inflammatory markers.