Potential impact of GCK, MIR-196A-2 and MIR-423 gene abnormalities on the development and progression of type 2 diabetes mellitus in Asir and Tabuk regions of Saudi Arabia

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by persistent hyperglycemia and is associated with serious complications. The risk factors for T2DM include both genetic and lifestyle factors. Genome-wide association studies have indicated the association of genetic variations with many diseases, including T2DM. Glucokinase (GCK) plays a key role in the regulation of insulin release in the pancreas and catalyzes the first step in glycolysis in the liver. Genetic alterations in the GCK gene have been implicated in both hyperglycemia and hypoglycemia. MicroRNAs (miRNAs/miRs) are small non-coding RNA molecules that are involved in the important physiological processes including glucose metabolism. In the present study, the association of the single nucleotide polymorphisms (SNPs) in the GCK, MIR-196A-2 and MIR-423 genes with susceptibility to T2DM in patients from two regions of Saudi Arabia were examined, using the tetra-primer amplification refractory mutation system. The results showed that the AA genotype and the A allele of GCK rs1799884 were associated with T2DM [odds ratio (OR)=2.25, P=0.032 and OR=1.55, P=0.021, respectively]. Likewise, the CT genotype and T allele of MIR-196A-2 rs11614913 were associated with an increased risk of T2DM (OR=2.36, P=0.0059 and OR=1.74, P=0.023, respectively). In addition, the CA genotype of MIR-423 rs6505162 C>A was found to be linked with T2DM (OR=2.12 and P=0.021). It was concluded in the present research study that gene variations in GCK, MIR-196A-2 and MIR-423 are potentially associated with an increased risk of T2DM. These results, in the future, may help in the identification and stratification of individuals susceptible to T2DM. Future longitudinal studies with larger sample sizes and in different ethnic populations are recommended to validate these findings.

The hypolipidemic mechanism of chrysanthemum flavonoids and its main components, luteolin and luteoloside, based on the gene expression profile

“…The results of our previous animal experiments also support the idea that the intervention group of CF improved the hepatic steatosis of hyperlipidemic rats ( 16 ). Gluckinase (GCK) is a key enzyme regulating insulin release and the first step in catalyzing glycolysis in the liver ( 20 ). Its genetic polymorphisms are associated with susceptibility to gestational diabetes.…”

Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression

“…Gradient PCR was performed using different annealing temperatures and a lesser number of cycles were used (25 to 30 cycles). This optimization was achieved in a series of optimization experiments in a single run by the gradient PCR machine following some previous reported studies [ 22 , 23 , 24 , 25 ]. The annealing temperature via gradient PCR was optimized from 58 °C to 62 °C, but the best results were obtained at a temperature 58 °C.…”

“…ARMS-PCR is based on the principle that the 3′-terminal nucleotides of the PCR primer must be complementary to its target sequence for efficient amplification. Amplification refractory mutation system PCR (ARMS-PCR) has been approved by the China Food and Drug Administration (CFDA) and has become a widely used method in clinical practice [ 23 , 24 ]. ARMS-PCR is more sensitive than Sanger sequencing due to its detection limit being about 1% [ 25 ].…”

miRNAs provide mechanisms for integrated control of endocrine pancreas homeostasis and metabolic disease pathogenesis: a narrative review

“…ExRNA 2022;4:24 | https://dx.doi.org/10.21037/exrna-22-17 or insulin secretion rates (11), the discovery of SNPs in miR-196a and miR-423 linked to increased risk of T2D in Middle East regions (193) or the identification of "unique" signatures in the miRNA profile during the progression of T2D, where for instance, miR-222-3p and miR-148-3p were specifically modulated in diabetic patients and correlated with clinical parameters of glucose and lipid metabolism (194). Interestingly, miR-148-3p, also found to be increased in the serum of T1D (195), is highly present in human and cow milk exosomes and it has been hypothetised as a modulator of beta cell de-differentiation-at the transition that takes place during weaning process-and to play a pathogenic role in T2D during adulthood (196) adding a new perspective on the roles of dietary miRNAs as bioactive components of food and their relevance on health and disease (197).…”