title: Impact of the hypoxia inducible factor-1α (HIF-1α) pro582ser polymorphism and its gene expression on diabetic foot ulcers.
abstract: OBJECTIVE
  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 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Prof. M. Viswanathan Diabetes Research Centre, MV Hospital for Diabetes, Royapuram, Chennai 600013, Tamil Nadu, India. Electronic address: au_sudha@yahoo.com.
authors.forename: Sivakamasundari
authors.initials: S
authors.lastname: Pichu
authors.affiliation: Prof. M. Viswanathan Diabetes Research Centre, MV Hospital for Diabetes, Royapuram, Chennai 600013, Tamil Nadu, India.
authors.forename: Jayalalitha
authors.initials: J
authors.lastname: Sathiyamoorthy
authors.affiliation: Prof. M. Viswanathan Diabetes Research Centre, MV Hospital for Diabetes, Royapuram, Chennai 600013, Tamil Nadu, India.
authors.forename: Ezhilarasi
authors.initials: E
authors.lastname: Krishnamoorthy
authors.affiliation: Prof. M. Viswanathan Diabetes Research Centre, MV Hospital for Diabetes, Royapuram, Chennai 600013, Tamil Nadu, India.
authors.forename: Dhamodharan
authors.initials: D
authors.lastname: Umapathy
authors.affiliation: Prof. M. Viswanathan Diabetes Research Centre, MV Hospital for Diabetes, Royapuram, Chennai 600013, Tamil Nadu, India. Electronic address: dr_vijay@mvdiabetes.com.
authors.forename: Vijay
authors.initials: V
authors.lastname: Viswanathan
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D017719:Diabetic Foot / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000235:genetics; D012694:Serine / Q000235:genetics
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012694:Serine; D011392:Proline
keywords: DFU; HIF-1α; Hypoxia; SNP; T2DM