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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.

SUBMITTER: Akash MSH

PROVIDER: S-EPMC9962810 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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

Akash Muhammad Sajid Hamid MSH Rasheed Sumbal S Rehman Kanwal K Ibrahim Muhammad M Imran Muhammad M Assiri Mohammed A MA

Metabolites 20230129 2

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 p ...[more]

PMID: 36837818

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Project description:Background and purposeThe study focuses on examining the relationship between a single nucleotide polymorphism (SNP) in KLF14 rs4731702 and risk of type 2 diabetes mellitus (T2DM) and dyslipidemia in different ethnic populations. The purpose of this study was to evaluate the association between KLF14 rs4731702 and serum lipid profile and to determine the frequency distribution of KLF14 rs4731702 among T2DM and cardiometabolic patients.MethodsA total of 300 volunteers were recruited, consisting of three groups: 100 healthy individuals, 100 individuals diagnosed with T2DM, and 100 individuals diagnosed with cardiometabolic disorders. Biochemical analysis of blood samples was conducted to assess various biomarkers related to glycemic control and lipid profile. This involved measuring levels of glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and ApoA1. Genotyping analysis was performed to investigate KLF14 rs4731702 polymorphism. The Tetra ARMS-PCR method was employed for genotyping analysis.ResultsThe results of biochemical profiling revealed a significant association between altered glycemic biomarkers and lipid profile in diseased patients compared to healthy participants. The frequencies of KLF14 rs4731702 alleles and genotypes were compared between the control group and T2DM group. A statistically significant difference was observed, indicating a potential association between KLF14 rs4731702 and T2DM. In the dominant inheritance model of KLF14 rs4731702 SNP, a statistically significant difference [odds ratio (95% confidence interval)] of 0.56 (0.34 -0.96) was found between the control and T2DM subjects. This suggests that the presence of certain genotypes influences the risk of T2DM. In T2DM patients, individuals carrying the C allele exhibited compromised insulin sensitivity, decreased HDL-C and ApoA1 levels, and increased serum glucose, TG, and LDL-C concentrations. Conversely, TT genotype carriers demonstrated increased levels of HDL-C and ApoA1, lower insulin resistance, serum glucose, LDL-C, and TG levels.ConclusionThe study's findings indicate that dyslipidemia in T2DM patients is associated with reduced KLF14 functionality due to CC and CT genotypes, leading to insulin resistance and an increased risk of cardiovascular diseases. Additionally, risk of KLF14 rs4731702 polymorphism was found to increase with age and was more prevalent in female than in male individuals. These insights contribute to understanding genetic factors influencing the development and progression of T2DM and dyslipidemia in different ethnic populations.

Project description:BackgroundCryptic genetic variation (CGV) is the hidden genetic variation that can be unlocked by perturbing normal conditions. CGV can drive the emergence of novel complex phenotypes through changes in gene expression. Although our theoretical understanding of CGV has thoroughly increased over the past decade, insight into polymorphic gene expression regulation underlying CGV is scarce. Here we investigated the transcriptional architecture of CGV in response to rapid temperature changes in the nematode Caenorhabditis elegans. We analyzed regulatory variation in gene expression (and mapped eQTL) across the course of a heat stress and recovery response in a recombinant inbred population.ResultsWe measured gene expression over three temperature treatments: i) control, ii) heat stress, and iii) recovery from heat stress. Compared to control, exposure to heat stress affected the transcription of 3305 genes, whereas 942 were affected in recovering animals. These affected genes were mainly involved in metabolism and reproduction. The gene expression pattern in recovering animals resembled both the control and the heat-stress treatment. We mapped eQTL using the genetic variation of the recombinant inbred population and detected 2626 genes with an eQTL in the heat-stress treatment, 1797 in the control, and 1880 in the recovery. The cis-eQTL were highly shared across treatments. A considerable fraction of the trans-eQTL (40-57%) mapped to 19 treatment specific trans-bands. In contrast to cis-eQTL, trans-eQTL were highly environment specific and thus cryptic. Approximately 67% of the trans-eQTL were only induced in a single treatment, with heat-stress showing the most unique trans-eQTL.ConclusionsThese results illustrate the highly dynamic pattern of CGV across three different environmental conditions that can be evoked by a stress response over a relatively short time-span (2 h) and that CGV is mainly determined by response related trans regulatory eQTL.

Dataset Information

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

Publications

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

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