HYPOXIA-INDUCIBLE FACTOR (HIF): STRUCTURE, FUNCTION AND GENETIC POLYMORPHISM

Abstract

Introduction. The review presents data on the structure and functions of hypoxia-inducible transcription factor - HIF. In today’s world, a person is constantly exposed to harmful damaging factors, the response of the body to which, depending on the state of adaptive systems leads either to the development of diseases or increase resistance. Important importance in the adaptation of the body to damaging effects belongs to the transcription factor, denoted as a hypoxia-inducible factor (HIF). There were identified more than 100 genes activated by HIF and therefore mediated by this transcription factor affecting the regulation of iron homeostasis, energy metabolism, the balance of Pro - and antioxidants in the cells, the activation of inhibitors of apoptosis and the formation of new blood vessels. The structure of HIF and its isoforms. The data on isoforms of HIF-α and organ-specific features of the distribution of HIF-1α, HIF-2α, and HIF-3α. Increased expression of α-subunits of transcription factor occurs in response to hypoxic effects, both acute and adaptive, psycho-emotional stress, under the action of toxic production-related factors. The increase in the level of HIF-α isoforms provides an expression of genes involved in the implementation of compensatory-adaptive responses to various harmful effects. Genetic polymorphism of the HIF. The data on the HIF-1α gene polymorphism and its association with various diseases are presented. It is shown that the most studied polymorphisms are rs11549465 C > T and rs11549467 T > C identified in the domain of oxygen-dependent degradation of the DNA sequence of the HIF-1α gene. Carriers of the C/T genotype have increased expression of HIF-1α transcription factor for rs11549465 C > T and rs11549467 T > Cpolymorphisms, Association with the risk of coronary heart disease and myocardial infarction is shown. The study of HIF-1α gene polymorphism can be promising for the diagnosis and prognosis of occupationally caused diseases, as well as the development of effective ways of their correction and prevention.