[Genetic determinants of cardiovascular remodeling in Uzbek patients with essential hypertension]

To study distribution of the incidence of polymorphic markers of the genes ACE (I/D), ANG (M235T), AT1R (A1166C), CYP11B2 (T344C) in patients with essential hypertension (EH) of Uzbek nationality; to determine carriage of gene combinations with detection of most unfavourable combinations associated with severity of cardiovascular remodeling.

We examined 172 Uzbek males with EH of the second-third degree, mean age 49.4 +/- 7.8 years, mean duration of EH 6.5 +/- 5.1 years. Polymorphism I/D, A1166C, M235T, T344C of genes ACE, AT1R, ANG, CYP11B2, respectively, was revealed in all the patients. The control group consisted of 60 Uzbek males matched by age. We performed echocardiography, duplex scanning of carotid arteries, dopplerography of the brachial artery, IEMA measurement of the level of vascular adhesion molecule VCAM-1S in blood serum, microalbuminuria in Micral-test. We isolated genome DNA, amplified polymorphic gene regions and analysed products of polymerase chain reaction.

Distribution of polymorphic markers of the genes ACE, CYP11B2, ANG, AT1R in EH Uzbek patients corresponds to this in Europeans. In most cases (95.4%) there was primarily combined carriage of "destroying" alleles of the genes of renin-angiotensin-aldosteron system associated with synergetic impact on development of left ventricular hypertrophy (LVH) and vascular remodeling; combination of alleles D+235T is most unfavourable in relation to severity of LVH, vasoregulatory endothelial dysfunction and is associated with the highest thickness of intima-media complex of the carotid artery. The role of 235T allele of ANG gene is most important in development of LVH.

Severity of vasoregulatory endothelial dysfunction is associated with carriage of both 235T allele of ANG gene and 1166C allele of AT1R gene, in the latter case aggravated by significant adhesion of vascular endothelium. Progression of atherosclerotic affection of the carotid arteries is associated more with carriage of D allele of ACE gene.