Genetic Polymorphism of the Nrf2 Promoter Region (rs35652124) Is Associated with the Risk of Diabetic Foot Ulcers. (17th August 2020)

• Record Type: Journal Article
• Authors: Teena, Rajan; Dhamodharan, Umapathy; Ali, Daoud; Rajesh, Kesavan; Ramkumar, Kunka Mohanram
• Other Names: Thomas Shane Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2020(2020)
• Publication Date: 2020-08-17
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2020/9825028
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : 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.