Abstract
Transcription factors (TF) are key proteins that are essential for initiation and regulation of gene expression. Hepatocyte nuclear factors (HNF) represent specific TF that regulate transcription of a wide variety of genes necessary for embryonic development and metabolic homeostasis.
The dysfunction of these TF is associated with diabetes mellitus and presumably with late diabetes complications. Heterozygous mutations in HNF1A, HNF4A and HNF1B genes cause monogenic diabetes (MODY ).
Polymorphisms in HNF1A and HNF4A contribute to the predisposition for type 2 diabetes mellitus and metabolic syndrome. The decrease of transcription activity of HNF-4á is associated with diabetic nephropathy, renotubular syndrome and increased risk of cardiovascular events and mortality (due to elevated plasma concentration of asymmetric dimethylarginine, discussed as a novel marker of endothelial dysfunction).
The elucidation of the roles of HNF significantly contributed to the understanding of the genetic aetiology of diabetes mellitus and facilitated individualized treatment of a patient with MODY. In future, they may become a potential pharmacological target for the treatment of type 2 diabetes.