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
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,
= 100), T2DM patients without complications (T2DM,
= 150), and healthy adults with normal glucose tolerance (NGT,
= 150). The subjects were genotyped by PCR-RFLP, and the polymorphism was identified by bidirectional Sanger sequencing. The expression of
,
,
, and
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),
= 0.01] and DFU [OR = 7.9 (4-14.9),
< 0.0001]. A significant decrease in transcriptional levels of
and
and a remarkable increase in
and
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.