Endocrine Abstracts

Objective: To establish possible associations of the polymorphism of the insulin receptor substrate−1 (IRS-1) gene with the severity of various components of metabolic syndrome in patients with arterial hypertension (AH). We examined 187 patients with AH aged 45–55 years (with history of hypertension less than 5 years, unsystematic administration of antihypertensive drugs and/or failure to achieve target blood pressure (BP) levels when prescribing drug therapy). The control group consisted of 30 individuals matched for age and sex.

Methods: Anthropometry, reactive hyperemia, color Doppler mapping, biochemical blood analysis, HOMA-insulin resistance (IR), glucose tolerance test, enzyme immunoassay (determined levels of adiponectin, interleukin-6 (IL-6), C-reactive protein (CRP)) and molecular genetic method (genotyping of polymorphic marker Gly972Arg of IRS-1gene).

Results: It was found that among the hypertensive patients, 103 had abdominal obesity, 43 – type 2 diabetes mellitus (established less than 2 years ago), 131 – increased blood triglycerides (≥150 mg/dL), 19 – decreased high density lipoproteins (HDL, <40 mg/dL in men and <50 mg/dL in women), 59 – prediabetes (33 – fasting hyperglycemia and 26 – impaired glucose tolerance), 126 had IR, assessed by the HOMA-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 practically 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). At the next stage, associations of the IRS-1 gene polymorphism with anthropometric, metabolic and hemodynamic parameters in hypertensive patients were evaluated. It was found that hypertensive patients with Arg/Arg and Gly/Arg genotypes had significantly higher levels of glucose (P<0.05), insulin (P<0.05), HOMA-IR (P<0.01), triglycerides (P<0.05) than patients with the Gly/Gly genotype. At the same time, body mass index, waist circumference, levels of BP, adiponectin, HDL, IL-6, CRP, total antioxidant activity, degree of endothelium-dependent vasodilation, as well as the frequency of occurrence of impaired glucose tolerance did not differ significantly with various IRS-1 genotypes.

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