Translational Biomedicine

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The Kruppel-Like Factor 14 (KLF14), Master Gene of Multiple Metabolic Phenotypes: Putative Trans-Regulator Network

Magellan Guewo Fokeng, Barbara Atogho-Tiedeu, Eugene Sobngwi, Jean-Claude Mbanya and Wilfred Fon Mbacham

Studies of genetics variants in the predisposition to metabolic diseases such as hypertension, dyslipidemias, obesity, diabetes and others related traits show their importance in the understanding of the disease pathophysiology. Many susceptibility genes are identified as associated to these diseases and in the case of type 2 diabetes mellitus (T2DM) and obesity, TCF7L2 (Transcription Factor 7 Like 2) and PPARG (peroxisome proliferator activated receptor gamma) genes are both associated by certain gene polymorphisms. These genes require a network of other genes to present particular phenotypes; in human pancreatic islets for example, ISL1 is a direct target of TCF7L2 and ISL1, in turn, regulates proinsulin production and processing via regulation of PCSK1 (proprotein convertase subtilisin/kexin type 1), PCSK2 (proprotein convertase subtilisin/kexin type 2), SLC30A8 (solute carrier family 30 member 8), MAFA (vmaf avian musculoaponeurotic fibrosarcoma oncogene homolog A), PDX1 (pancreatic and duodenal homeobox 1) and NKX6.1 (NK6 homeobox 1). Furthermore, TCF7L2 might also influence hepatic clearance of insulin via its effect on SLC30A8. As a master trans-regulator related to multiple metabolic phenotypes, KLF14 gene encode for Krüppel-like Factor 14 which is a transcription factor and previously shown by an genome wide association study (GWAS) to be associated with T2DM et high density lipoprotein (HDL) cholesterol levels. This gene constitutes a target for the future understanding of pathophysiological complications and regulation of the metabolic syndrome. This review identifies a network of genes whose expression is associated with KLF14 gene regulation in trans. The protein-protein interactions in the KLF14 protein network may provide a framework for understanding the implication of KLF14 gene in diseases risks.