Journal
ARCHIVES OF MEDICAL RESEARCH
Volume 52, Issue 2, Pages 224-232Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.arcmed.2020.10.011
Keywords
Nrf2; Diabetes; Post-translational modification; Angiogenesis; Foot ulcers; Single nucleotide polymorphisms
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Funding
- SRM-DBT Partnership Platform for Contemporary Research Services and Skill Development in Advanced Life Sciences Technologies'', Department of Biotechnology, Govt. of India [BT/PR12987/INF/22/205/2015]
- SRM Institute of Science and Technology, Kattankulathur, Tamilnadu, India
- King Saud University, Riyadh, Saudi Arabia [RSP-2020/165]
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The study indicates that the NRF2 gene polymorphism rs182428269 is associated with the pathogenesis of type 2 diabetes and diabetic foot ulcers, with the homozygous mutant (TT) genotype significantly increasing the risk of developing diabetes and foot ulcers.
Background. The pivotal role of Nuclear factor erythroid-2-related factor 2 (NRF2) in redox homeostasis and wound healing has been well documented. However, the genetic mechanisms that regulate NRF2 in type 2 diabetes and diabetic foot ulcers remain unexplored. The present study investigated the association of single nucleotide polymorphism rs182428269 (-127 C/T) in subjects with type 2 diabetes and diabetic foot ulcers. Methods. This cross-sectional study comprised 400 participants that included group I: normal glucose tolerant subjects (NGT, n = 150), group II: type 2 diabetes mellitus subjects (T2DM, n = 150) and group III: infected diabetic foot ulcer subjects (DFU, n = 100). The non-synonymous SNP rs182428269 was selected based on in silico analysis and genotyped by PCR-restriction fragment length polymorphism (RFLP) followed by bidirectional Sanger sequencing. In addition, the gene expression of NRF2 in patients with polymorphism was analyzed by qPCR to evaluate the functional impact of the SNP. Results. NRF2 expression was significantly decreased among the T2DM and DFU subjects when compared to the NGT subjects. Of particular interest, the homozygous mutant (TT) genotype of rs182428269 polymorphism was significantly associated with an increased risk for the development of T2DM (OR = 1.95 (1.02-3.72), p = 0.04) and DFU (OR = 5.66 (2.98-10.76), p = 0.0001). Furthermore, a progressive decline in NRF2 expression was observed among the T2DM and DFU subjects with TT genotype compared to the CC and CT genotypes. Conclusion. NRF2 polymorphism rs182428269 is associated with the pathogenesis of T2DM and DFU. (C) 2021 IMSS. Published by Elsevier Inc.
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