ANGIOTENSINOGEN POLYMORPHISM M235T IN PATIENTS WITH ESSENTIAL HYPERTENSION FROM THE REPUBLIC OF MACEDONIA
Najdanovska N1, Koceva S1,*, Zafirovska K2, Blagoevska M3, Kocova M1
*Corresponding Author: Professor Dr. Mirjana Kocova, Pediatric Clinic, Department of Endocrinology and Genetics, Vodnjanska 17, 1000 Skopje, Republic of Macedonia; Tel.: +389-2-111-713; Fax: +389-2-176-167; E-mail: ozonunit@unet.com.mk
page: 21

INTRODUCTION

Essential, primary or idiopathic hypertension is de­fined as a state of blood pressure above 140/90 mm Hg, which excludes the secondary forms of hypertension such as renovascular hypertension, renal parenchymal disease, pheochromocytoma, aldosteronism, or monogenic Mendel­lian forms of hypertension. Ninety-five percent of all cases of hypertension belong to the essential hypertension type [1]. Around 20% of adults over 40 years of age have blood pressure above 140/90 mm Hg. Their risk for stroke is 100% higher compared to normotensive individuals [2].

Essential hypertension is a multifactorial trait. The large number of intermediate phenotypes of essential hy­pertension appear as a result of a complex interaction of genetic and non genetic factors known as hypertension­ogenic factors, such as increased consumption of salt or alcohol, body mass index (BMI) above 26 kg/m2, de­creased physical activity and continuous stress. Hyper­tensinogenic factors should be taught to persons at-risk in order to prevent and control essential hypertension. It is likely that several genes interact with environmental fac­tors to produce high blood pressure in susceptible persons.

 

Studies of families and twins imply that 20-40% of essential hypertension may have a genetic basis. Poly­morphisms and mutations, such as the ACE gene,

b2 adrenergic receptor a adducin, angiotensinase X, rennin-binding protein, G protein b3 subunit, atrial natriuretic peptide and insulin receptor, are linked to essential hyper­tension but this association is usually weak [3]. The rennin-angiotensin system plays a key role in salt and water homeostasis and the maintenance of vascular tone. Rennin cleaves the angiotensinogen to produce angioten­sin 1 that is subsequently cleaved by ACE to produce angiotensin 2, a peptide hormone that causes vasocon­striction and salt retention. Therefore, genes encoding the components of RAS are attractive candidates for the in­vestigation of the genetic basis of essential hypertension.

 

 

Many researchers have tested the association of angio­tensinogen polymorphism M235T and essential hyperten­sion. The M235T polymorphism has been linked to essen­tial hypertension in-affected sibships. In study populations from Paris, France and Utah, USA, 15 polymorphisms of the angiotensinogen gene (1q42-43) were identified. How­ever, only one, on exon 2 with threonine instead of meth­ionine at position 235 (M235T) was found to be signifi­cantly associated with essential hypertension [4]. By se­quencing a 14.4 kb genomic region 44 polymorphisms of angiotensinogen gene have been identified [5]. However, although many studies of the association of M235T and essential hypertension have been conducted, no consistent results have so far been obtained. In this study, we ana­lyzed the association of angiotensinogen polymorphism M235T in a group of patients from the Republic of Mace­donia, selected by strict inclusion criteria.

 




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