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Complex of metabolic disorders in hypertensive patients: clinical-genetic characteristic


Author: Curocichin Ghenadie
Degree:doctor habilitat of medicine
Speciality: 14.00.05 - Internal Diseases (with specification: Pulmonology, Gastroenterology, Hepatology, Nephrology, Functional Diagnostics and Endoscopy)
Year:2009
Scientific consultants: Vlada-Tatiana Dumbrava
doctor habilitat, professor, State University of Medicine and Pharmacy "Nicolae Testemitanu"
Nicolae Barbacar
doctor habilitat, professor, Institute of Genetics and Plant Physiology of the ASM
Institution:
Scientific council:

Status

The thesis was presented on the 4 March, 2009
Approved by NCAA on the 18 June, 2009

Abstract

Adobe PDF document0.68 Mb / in romanian

Thesis

CZU 616.12-008.331.1-008.9-056.7

Adobe PDF document 1.39 Mb / in romanian
206 pages


Keywords

glucose metabolism, metabolism of lipids, obesity, insulin resistance, diabetes mellitus, arterial hypertension, cardiovascular complications, candidate genes, genetic polymorphism

Summary

Cardiovascular diseases and type 2 diabetes mellitus (T2DM) have common modifiable (obesity, dislipidemia, arterial hypertension (AH), impaired glucose tolerance, behavioral factors) and non-modifiable (age, sex, aggravated heritability) risk factors. It has been presumed that abnormalities comprising the metabolic syndrome (MS) are pivotal for growing cardiovascular morbidity and cause increased risk of T2DM.

The prevalence by addressability and specific features of complex of the metabolic abnormalities in hypertensive patients related to candidate gene polymorphism have been investigated in order to improve early diagnosis of metabolic disorders at different stages of medical care.

As a result of clinical, instrumental and laboratory examination of 1025 patients who visited primary care institutions and 251 hypertensive patients, who underwent additional molecular-genetic examination, it was revealed that prevalence of MS according to addressability data is 23,7%, and is 38,7% in hypertensive patients. The prevalence of MS raises with age, and its presence increases relative risk of T2DM by 5,57 times, relative risk of stroke by 2,13 times, and relative risk of myocardial infarction (MI) by 5,55 times. Most robust results in positive diagnosis of the MS, independently of classification applied, are produced by insulin resistance evaluation using serum insulin concentrations.

It has been established that in carriers of D allotype of the angiotensin-converting enzyme (ACE) 3 and more components of MS are found twice as frequent as in non-carriers, and these patients have a tendency to have stroke more often. Carriage of CC genotype of type 1 angiotensin II receptor (AGTR-1) is linked to higher degrees of obesity and increased frequency of stroke, whereas carriage of AC genotype is associated with presence of multiple components of MS and more advanced impairment in glucose and lipid metabolism.

Presence of Asp/Asp genotype of NO-synthase (NOS) is related to more advanced degrees of obesity, higher levels of blood pressure (BP), and increased risk of stroke. Carriage of NOS allotype b in hypertensives is associated with more pronounced abdominal obesity, more advanced carbohydrate metabolism impairment, and T2DM as well as with increased risk of MI, whereas presence of NOS genotype aa is associated with extremely high blood pressure, and with tendency to more frequent strokes.

In case of VNTR polymorphism of insulin gene, carriage of I allele in homozygote form I/I is associated with elevated BP and multiple disturbances comprising the metabolic syndrome. Carriage of allele III in homozygote form III/III is associated with increased frequency of MI in hypertensives. Presence of R allele of insulin receptor substrate 1 (IRS-1) is significantly associated with extreme obesity, hyperglycemia, and T2DM. Presence of I allotype in homozygous form I/I is significantly associated with increased risk of MI.

It has been demonstrated that polymorphism of interleukin-6 (IL-6) gene is involved in MS development via mechanisms of carbohydrate and lipid metabolism regulation: carriage of B allotype is associated with highest degrees of obesity, and presence of A allotype is associated with multiple metabolic disturbances comprising the MS, and especially with hypertriglyceridemia, hyperglycemia, and T2DM.

Based on the results obtained in the research, practical recommendations for clinical detection of the MS at primary, secondary, and tertiary care levels were elaborated aimed at improvement of detection of complex metabolic disorders and early prevention of complications.