AKU Researchers Unravel Genetics of High Blood Pressure

Professor Philippe Frossard, Director of the GMCD Group and Chair, Department of Biological and Biomedical Sciences, with his team of researchers.

Essential hypertension, or elevated blood pressure of unknown cause, is a major health problem in Pakistan, affecting 18 per cent of adults over the age of 15 and one out of every three persons over 45. It represents a significant risk for heart attack, stroke and kidney failure. While the condition can be traced to 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 per cent or less of patients, indicating a poor match between pharmacological action and the underlying molecular mechanisms of the 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 form a class of anti-hypertensive drugs known as ACE inhibitors and are often used in the treatment of essential hypertension.

One of the major problems associated with the treatment of hypertension is the lack of an effective determinant for which drugs should be used. The University's 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 elevated ACE levels in people inheriting a particular variant of the gene may participate in the determination of an individual's genetic susceptibility to the disease.

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 Chief Coordinator of the GMCD Group and Director of this project. Other key scientists involved in the project were Dr Syed Osman Ali, Instructor in BBS, and Kausar Saboohi, Senior Technologist, BBS. The study was carried out in its entirety at AKU's state-of-the-art research laboratories. 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.