Association of IRS-1 polymorphism with various components of the metabolic syndrome in hypertensive patients

Abstract

Introduction: The metabolic syndrome is one of the most discussed cross-disciplinary problems of modern medicine. Now there are various definitions and criteria of diagnostics of metabolic syndrome. The abdominal obesity is considered the main component of the metabolic syndrome, as a reflection of visceral obesity which degree is offered to be estimated on an indirect indicator – a waist circumference. Alongside with abdominal obesity, a number of classifications distinguish insulin resistance (IR) as a diagnostic criterion of metabolic syndrome. It is proved that IR is one of the pathophysiological mechanisms influencing the development and the course of arterial hypertension (AH), type 2 DM and obesity. There are two components in the development of IR: genetic (hereditary) and acquired. In spite of the fact that IR has the accurate genetic predisposition, exact genetic disorders of its appearance have not been identified yet, thus demonstrating its polygenic nature.

The aim: To establish possible associations of the insulin receptor substrate-1 (IRS-1) gene polymorphism with the severity of the metabolic syndrome components in patients with arterial hypertension (AH). Materials and methods: 187 patients with AH aged 45-55 years and 30 healthy individuals. Methods: anthropometry, reactive hyperemia, color Doppler mapping, biochemical blood analysis, HOMA-insulin resistance (IR), glucose tolerance test, enzyme immunoassay, molecular genetic method.

Results: Among hypertensive patients, 103 had abdominal obesity, 43 - type 2 diabetes, 131 - increased blood triglycerides, 19 - decreased high density lipoproteins, 59 - prediabetes (33 - fasting hyperglycemia and 26 - impaired glucose tolerance), 126 had IR. At the same time, hypertensive patients had the following distribution of IRS-1 genotypes: Gly/Gly - 47.9%, Gly/Arg - 42.2% and Arg/Arg - 10.7%, whereas in healthy individuals the distribution of genotypes was significantly different: Gly/Gly - 86.8% (p<0.01), Gly/ Arg - 9.9% (p<0.01) and Arg/Arg - 3.3% (p<0.05). Hypertensive patients with Arg/Arg and Gly/Arg genotypes had significantly higher HOMA-IR (p<0.01), glucose, insulin and triglycerides levels (p<0.05), than in Gly/Gly genotype. At the same time, body mass index, waist circumference, blood pressure, adiponectin, HDL, interleukin-6, C-reactive protein, degree of endothelium-dependent vasodilation, as well as the frequency of occurrence of impaired glucose tolerance did not significantly differ in IRS-1 genotypes.

Conclusions: in hypertensive patients, the genetic polymorphism of IRS-1 gene is associated with such components of the metabolic syndrome as hypertriglyceridemia and fasting hyperglycemia; it is not associated with proinflammatory state, endothelial dysfunction, dysglycemia, an increase in waist circumference and decrease in HDL.