[PP.29.01] FEATURES OF METABOLIC HOMEOSTASIS DEPENDING ON GENETIC POLYMORPHISM OF INSULIN RECEPTOR SUBSTRATE-1 GENE IN PATIENTS WITH ESSENTIAL HYPERTENSION UNDER COMORBIDITY

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Abstract

Objective:

To investigate the features of metabolic homeostasis in various polymorphism of insulin receptor substrate-1 (IRS-1) gene in patients with essential hypertension (EH), obesity and type 2 diabetes (DM2).

Design and method:

The main group consisted of 215 patients with EH, obesity and DM2. The comparison group consisted of 50 patients with EH and obesity without DM2. The control group consisted of 31 healthy individuals.

Design and method:

We determined carbohydrate and lipid profiles, HOMA-IR, levels of leptin, malondialdehyde (MDA), catalase, conducted genotyping of polymorphic marker Gly972Arg of IRS-1 gene.

Results:

It was established that in patients with EH and obesity both as in presence and absence of DM2, the frequency of Gly/Arg and Arg/Arg genotypes was significantly higher than in control group (p < 0.001).

Results:

The presence of Gly/Arg and Arg/Arg genotypes of IRS-1 gene in patients of the main group was associated with higher levels of atherogenic lipoproteins (p < 0,001). The association of Gly972Arg polymorphism with the development of insulin resistance (IR) was also confirmed significant higher levels of insulin, HOMA-IR, glucose (p < 0,001), HbA1c (p < 0,05) in presence of Gly/Arg and Arg/Arg genotypes. In these genotypes patients of the main group had significantly higher levels of leptin, of oxidative stress indicator MDA and significantly lower levels of antioxidant system indicator catalase (p < 0,05) as compared to Gly/Gly genotype.

Results:

Patients with EH and obesity without DM2 in presence of Gly/Arg and Arg/Arg genotypes had significantly higher levels of atherogenic lipoproteins, insulin and HOMA-IR (p < 0,01), than patients with Gly/Gly genotype, however, unlike patients with DM2, they had no significant difference of leptin, MDA and catalase.

Conclusions:

It was established that IRS-1 gene polymorphism was associated with the development of comorbidity EH, obesity and DM2. Arg/Arg and Gly/Arg genotypes of IRS-1 gene in patients with EH and obesity both as in presence and absence of DM2 were associated with more pronounced disorders of blood lipid spectrum, more pronounced IR as compared to Gly/Gly genotype. Significant differences of leptin levels and indicators of oxidative stress - antioxidant protection depending on IRS-1 gene polymorphism were established only in presence of DM2 in patients with EH and obesity.

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