Impact of the hypoxia inducible factor-1α (HIF-1α) pro582ser polymorphism and its gene expression on diabetic foot ulcers

Aim: Adaptation to low oxygen tension (hypoxia) in cells and tissues leads to the transcriptional induction of series of genes and the primary factor mediating this response is the hypoxia-inducible factor-1 alpha. This study was designed in order to examine the HIF-1 alpha gene polymorphism, p582s (rs11549465) in Exon-12 of HIF-1 alpha gene in diabetic subjects with and without foot ulcers (DFU) and to find its expression under these pathological conditions. Methods: A total of 224 subjects from our tertiary care centre were included, which consists of healthy controls (N = 66), type 2 diabetes mellitus (T2DM) (N = 79) and T2DM with foot ulcers (DFU) (N = 79). Allelic and genotypic comparisons between the different groups were evaluated by PCR-RFLP. The gene expression studies on selected samples (N = 15 of each group) were done by Semi-quantitative real time PCR. Results and discussions: Genotype analysis showed a significant increase in presence of 'T' allele in T2DM & DFU when compared to that of control subjects. Allele wise analysis showed a higher frequency of 'T' allele in the T2DM (62.03%) when compared to that of control subjects (53.79%). Interestingly, semi-quantitative RT-PCR results showed decreased expression of HIF-1 alpha gene on DFU when compared to that of T2DM and control subjects. Conclusion: Our findings predict that there is an association of HIF-1 alpha gene polymorphism on foot ulcer patients when compare to that of healthy controls. Semi-quantitative real time studies showed decreased HIF-1 alpha gene expression on foot ulcer patients suggesting its possible role on the pathogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.