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.

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