Hypoxia Inducible Factor-1α Gene rs11549465 Might be Protective Factor for the Development of Type 1 Diabetes Mellitus

Introduction: Pancreas is a highly vascularized tissue which makes oxygen a fundamental element for its metabolism. As a consequence of the variations in its delivery, the expression of genes that maintain homeostatic levels of oxygen supply a regulated by hypoxia-inducible factor 1 α (HIF-1α). Here we tested the role of single nucleotide polymorphism (SNP) of HIF-1α as markers for susceptibility or protection to develop pancreatic injury in Mexican patients with type 1 diabetes mellitus (T1DM).
Methods: We studied 55 patients with T1DM that conformed to the criteria of the American Diabetes Association (ADA); in them, we extracted DNA from peripheral blood cells and studied the gene that encodes HIF-1α. The SNP selection was done in accordance to the SNP database (https://www.ncbi.nlm.nih.gov/SNP/). Three polymorphisms were included: rs11549465, rs11549467 and rs2057482. Statistical analysis was performed by the EpiInfo statistical program (version 6), using p<0.05 as the level as statistical significance; gene frequencies were compared to those present in 66 healthy ethnically matched individuals.
Results: We observed in patients a significant decreased frequency of the polymorphism rs11549465 as compared to the group of healthy controls (p=0.0018; OR=0.07 [0.0-0.48]). We observed a change in the domain oxygen dependent degradation domain “ODDD” which converts Pro-582 to Ser.
Conclusion: The T allele of the polymorphism rs11549465 seems to be a protective factor for the development of T1DM.