HIF1A gene polymorphisms and human diseases: Graphical review of 97 association studies

Hypoxia-inducible factors (HIFs) belong to a family of transcription factors (TF) responsive to a low O-2 availability, which is often a characteristic feature of solid tumors. The alpha subunit of the HIF heterodimer is O-2-sensitive, and once stabilized in hypoxia, it functions as a master regulator of various genes involved in hypoxia pathway. Changes in the HIF1A (hypoxia inducible factor 1, alpha subunit) nucleotide sequence or expression has been shown to be associated with the development of several diseases. Because of increasing research interest in HIF1A gene a review of association studies was needed. We here reviewed published data on single nucleotide polymorphisms (SNPs) in HIF1A in various diseases; in total, 34 SNPs were tested for an association with 49 phenotypes, and the results were visualized using the Cytoscape software. Among all collected polymorphisms 16 SNPs showed significant associations with 40 different phenotypes, including six SNPs associated with 14 cancer types. Missense SNPs (rs11549465 and rs11549467) within the oxygen-dependent degradation domain were most frequently studied. The study provides a comprehensive tool for researchers working in this area and may contribute to more accurate disease diagnosis and identification of therapeutic targets.