Biochemical Activation and Regulatory Functions of Trans-Regulatory KLF14 and Its Association with Genetic Polymorphisms

Abstract

Krüpple-Like family of transcription factor-14 (KLF14) is a master trans-regulatory gene that has multiple biological regulatory functions and is involved in many pathological mechanisms. It controls the expressions of several other genes which are involved in multiple regulatory functions. KLF14 plays a significant role in lipid metabolism, glucose regulation and insulin sensitivity. Cell apoptosis, proliferation, and differentiation are regulated by the KLF14 gene, and up-regulation of KLF14 prevents cancer progression. KLF14 has been used as an epigenetic biomarker for the estimation of chronological age due to the presence of different age-related CpG sites on genes that become methylated with age. Different genome-wide association studies have identified several KLF14 variants in adipose tissues. These single nucleotide polymorphisms in KLF14 have been associated with dyslipidemia, insulin resistance, and glucose intolerance. Moreover, the prevalence of genetic polymorphism is different in different populations due to ethnic differences and epigenetic modifications. In addition, environmental and physiological factors such as diet, age, gender, and obesity are also responsible for genetic mutations in KLF14.

Association of KLF14 rs4731702 gene polymorphism with metabolic phenotype in young patients with type 1 diabetes

“…9,13 Multiple studies indicate that epigenetic alterations within the KLF14 gene could be implicated in the onset of metabolic disorders. 1,13,14 Moreover, the expression levels of KLF14 have been observed to vary throughout the advancement and emergence of metabolic conditions. 13 The most extensively studied single nucleotide polymorphism (SNP) in the KLF14 gene is rs4731702.…”

“…1,13,14 Moreover, the expression levels of KLF14 have been observed to vary throughout the advancement and emergence of metabolic conditions. 13 The most extensively studied single nucleotide polymorphism (SNP) in the KLF14 gene is rs4731702. This SNP has been associated with various metabolic conditions, including body mass index (BMI), lipid levels, and insulin sensitivity.…”

“…It is located within an intron of the KLF14 gene and has been demonstrated to influence gene regulation, potentially impacting metabolic diseases such as T2D, obesity, and metabolic syndrome. 13,14 While other SNPs in or near the KLF14 gene may hold significance, they have not been as widely implicated in specific metabolic traits. Although noted in genome-wide association studies (GWAS), some associations between KLF14 SNPs and specific traits or diseases are not as well defined as those observed for rs4731702.…”

“…Although noted in genome-wide association studies (GWAS), some associations between KLF14 SNPs and specific traits or diseases are not as well defined as those observed for rs4731702. 13 KLF14 is also involved in regulating the inflammatory response. It may modulate the expression of genes involved in inflammation by interacting with other transcription factors or regulatory elements within the genome.…”

“…It may modulate the expression of genes involved in inflammation by interacting with other transcription factors or regulatory elements within the genome. 1,3,[13][14][15] Additionally, the gene has been found to be expressed in immune cells, such as macrophages, which are important cells of inflammatory response. 16 KLF14 was shown to have antiinflammatory activity in atherosclerotic endothelial cells by inhibiting the nuclear factor kappa-B signalling pathway.…”