Aga Khan University (AKU) genetic researchers have pinpointed a gene involved in the modulation of high blood pressure. This new finding will make it possible to predict which individuals will respond to particular treatments better. It may also contribute to form the basis for the development of genetic tests aimed at assessing an individual's genetic susceptibility to essential hypertension.

Essential hypertension, or elevated blood pressure of unknown cause, is a major health problem in Pakistan, affecting 18% of the adult population over 15 years of age, and one out of every three persons over 45 years. It represents a significant risk for heart attack, stroke, and kidney failure. While the condition has genetic causes, environmental factors such as diet, stress and exercise contribute to its development. This complex interplay of variable factors has so far eluded most attempts at identifying the molecular basis of essential hypertension. While various drugs are available for blood pressure control, any one drug is effective in only 50% or less of the patients, indicating a poor match between pharmacological action and the underlying mechanism of disease.

The "Gene Markers and Complex Disorders" (GMCD) Research Group at AKU, has found that an individual variation in the angiotensin-converting enzyme (ACE) gene is associated with an inherited tendency to develop high blood pressure. The ACE gene is involved in generating the active form of the hormone angiotensin II, which plays a major role in the regulation of vascular tone and blood volume - the two key determinants of blood pressure. Drugs that inhibit the formation of angiotensin II by blocking ACE are often used in the treatment of essential hypertension (they form a class of anti-hypertensive drugs known as "ACE Inhibitors").

One of the major problems associated with treatment of hypertension is that currently there is no effective determinant for which drugs should be used. This research into the ACE gene has resulted in the identification of a genetic marker for hypertension, which may be used as part of a genetic test for more specifically identifying patients who are likely to benefit from ACE inhibitor therapy. The work provides clues to the molecular mechanisms underlying hypertension, and suggests that an individual's genetic susceptibility may result from elevated ACE levels in people inheriting a particular variant of the gene.

The work was led by Professor Philippe Frossard, Director of the GMCD Group and Chair, Department of Biological and Biomedical Sciences (BBS) at AKU, and Dr. Mohammad Saeed, Instructor in BBS, who is also the Chief Coordinator of the GMCD Group and the Director of this project.. Other key scientists involved in the project were Dr. Syed Osman Ali, Instructor in BBS,

and Kausar Saboohi, Senior Technologist in BBS. The work was entirely done in the state-of-the-art research laboratories at AKU. The GMCD Group is involved in further research endeavours to tease out the molecular and genetic architectures of cardiovascular disorders such as hypertension, stroke, diabetes and myocardial infarction, which are the leading causes of morbidity and mortality worldwide.