Angiotensin converting enzyme gene polymorphism and hypertension: no ace yet in the pack of cards.

S ystemic hypertension remains an important risk factor for a variety of cardiovascular, renal and neurological diseases. It is well known that elevated blood pressure (BP) of any degree is a precursor to excessive morbidity and premature mortality. untreated hypertension predisposes to coronary artery disease (CAD), left ventricular hypertrophy (LVH), congestive heart failure (CHF), chronic kidney diseases (CKD), end-stage renal disease (ESRD), transient ischemic attacks (TIA), and cerebrovascular accidents (CVA). Although systemic hypertension is a risk factor for disease burden, the risk is uneven, heterogeneous, and unpredictable. At the present time, there is no way to determine which patient with an elevated blood pressure (BP) level is at risk and which patient is not; therefore, BP level reduction is indicated and recommended for " all " individuals with hypertension irrespective of their " personal risk ". Hence guidelines rightly recommend measures to reduce the BP in all persons with hypertension. Despite successful treatment of hypertension, some patients experience complications whereas other patients remain free of disease even though their hypertension remains untreated or uncontrolled. This clinical scenario, therefore, raises the possibility of " genetics " in the development of hypertension and/or related complications. Various " genetic " hypotheses have been proposed to explain systemic hypertension but none has been clearly identified. Monogenic explanations have not stood the test of evidence. Hence, it is possible (but not proven) that hypertension may be of polygenic origin. To define hypertension beyond numbers, much work has been done in the areas of genetics, inheritance, and environmental factors. In the current issue of JAPI, Borah and co-workers 1 show evidence that in the northeastern state of Assam, India, Angiotensin Converting enzyme (ACe) gene polymorphism is linked to isolated systolic hypertension (ISH). Renin-Angiotensin-Aldosterone-System (RAAS) is one of the regulatory systems governing circulation, systemic vascular resistance, and kidney function. Thus, it is logical to assume that inappropriate activation of RAAS elevates systemic BP and may be an aetio-pathologic factor in the genesis of hypertension. An upward aberration in the activity of RAAS might lead to an upward shift in the BP level. For the same reason pharmacological measures which block RAAS are widely used to treat hypertension. ACe is a dipeptidyl carboxy-peptidase-I which activates angiotensin-I through cleavage of carboxy-terminal dipeptide into angiotensin II which causes vasoconstriction and subdues the activity of vasodilators such as bradykinin. Imbalance between forces of vasoconstriction over forces of vasodilation elevates the systemic …