FUNCTIONAL ROLE OF THE TP53 GENE SINGLE NUCLEOTIDE POLYMORPHISM P72R (C>G) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS OF THE EAST UKRAINIAN POPULATION

Abstract

Recently, the role of stress-regulatory pathways in the development and progression of type 2 diabetes mellitus (T2DM) and associated cardiovascular diseases has been widely investigated. The aim of the study was to assess the relationship of polymorphic variants P72R (C>G) of the TP53 gene with the functional and metabolic characteristics of type 2 diabetic patients in the East Ukrainian population. Materials and methods. 50 T2DM patients (female/male: 21/29) aged 53.34±1.43 yrs., with diabetes duration of 6.25±0.89 yrs., HbA1c level of 7.12±0.21%, body mass index of 31.19±0.93 kg/m², with waist-to-hip ratio of 0.96±0.01, with the presence of coronary heart disease in 38 cases, hypertension in 46 cases, and their combination in 37 cases. Characteristics of carbohydrate/lipid metabolism, parameters of insulin resistance, chronic inflammation, and a number of adipokines were determined in the subjects. Genotyping for single nucleotide polymorphism P72R (C>G) TP53 was performed by the method of polymerase chain reaction with appropriate primers and BstUI endonuclease. Testing of null hypotheses was carried out using the t, F and c² criteria at the significance level of P≤0.05.

Results. There was a noticeable tendency (P=0.05) to increase in frequency of the recessive allele G, mainly in men, which requires further extended studies. In addition, carriers of the minor genotype are characterized by a significantly younger age of T2DM manifestation. Under the statistically similar parameters that characterize the degree of obesity and glucose metabolism compensation, the connection of the G-allele with insulin resistance, both hepatic (HOMA-IR) and associated with adipose tissue (HOMA-IR/adiponectin, adiponectin/leptin) was observed. Carriers of the recessive allele are also characterized by an increased atherogenic coefficient relative to the dominant CC genotype, a significant decrease in the levels of adiponectin (total and high molecular weight) and omentin, and an increase in the levels of leptin and vaspin in the circulation. According to the recessive model, the presence of the G-allele is accompanied by a weak but probable increase in the levels of highly sensitive C-reactive protein (CC vs. CG+GG: 1.92±0.42 mg/l vs. 4.62±0.94 mg/l, P <0.05). The above suggests that the G-allele may be a predictor of a greater risk of cardiovascular disease development in patients with T2DM.

Conclusions. It has been proven that the P72R polymorphism of the TP53 gene is functional for the East Ukrainian population, because against the background of a comparable degree of obesity and glucose metabolism compensation, carriers of the minor G-allele are characterized by a greater degree of insulin resistance and a proatherogenic shift in the hormonal activity of adipose tissue. A tendency to increase in frequency of the G-allele in men with type 2 diabetes was revealed, and it was determined that carriers of the minor genotype are characterized by a significantly younger age of diabetes manifestation. The obtained results substantiate the need for further research to assess the role of this polymorphism in the Ukrainian population.