
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
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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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