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Impact of the hypoxia inducible factor-1α (HIF-1α) pro582 ser polymorphism and its gene expression on Diabetic foot ulcers
Sivakamasundari Pichu , Jayalalitha Sathiyamoorthy, Ezhilarasi Krishnamoorthy, Dhamodharan Umapathy, Vijay Viswanathan,
Diabetes Research and Clinical Practice; 22 May 2015
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-1α. This study was designed in order to examine the HIF-1α gene polymorphism, p582s (rs11549465) in Exon-12 of HIF-1α 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 Diabetic 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-1α gene on DFU when compared to that of T2DM and Control subjects.
Conclusion
Our findings predict that there is an association of HIF-1α gene polymorphism on foot ulcer patients when compare to that of healthy controls. Semi-quantitative real time studies showed decreased HIF-1α gene expression on foot ulcer patients suggesting its possible role on the pathogenesis.
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