When the drugs don't work

A University of Glasgow researcher has been awarded a fellowship of over £256k from the British Heart Foundation (BHF) to map a genetic location that explains why certain blood pressure-lowering drugs are not effective for some patients.

"The findings bring us a step closer to developing targeted therapies for patients with high blood pressure who might otherwise be started on medications that won't help," explains Dr Sandosh Padmanabhan, BHF Intermediate Fellow and Senior Lecturer at the newly launched BHF Glasgow Cardiovascular Research Centre at the University of Glasgow.

High blood pressure (hypertension) is a major risk factor for heart disease, stroke and kidney disease. Most patients require two or more medications to achieve optimal blood pressure control which reduces the risk of developing complications.

However, only a quarter of hypertensive patients achieve optimal blood pressure control despite there being more than a hundred anti-hypertensive drugs. This can be attributed partly to individual differences in the response to anti-hypertensive therapy, partly to non-compliance, and partly to side-effects that contribute to withdrawal of treatment. Finding genes that determine a patient's response to anti-hypertensive medications is critical for effective therapy and also for understanding the cause of the hypertension in specific individuals.

Dr Padmanabhan continues: "We studied 2,142 severely hypertensive sibling pairs as part of the Medical Research Council's British Genetics of Hypertension (BRIGHT) study, and identified a region on human chromosome 2 which may contain genes that determine whether a patient responds or fails to respond to a specific group of hypertension medications.

"This is the first study to demonstrate a chromosomal region linked to drug response in hypertension. The results of our pilot study look promising and will be a key step in the progress towards identifying patient characteristics that determine drug response and efficiency.

"Identification of the causative gene or gene sequence in this region will help target the right drug to the right patient and will have a considerable impact on public health in addition to greatly expanding our understanding of the causation of hypertension.

"The British Heart Foundation (BHF) have been generous enough to award me a 3 year intermediate fellowship to take this study forward and try to pinpoint the exact gene or genes responsible for this drug response."

The newly opened BHF Glasgow Cardiovascular Research Centre, core funded by a gift of £5M from the BHF, will provide state-of-the-art laboratory and clinical facilities to further vital research into cardiovascular disease. The proximity of a clinical investigation unit to modern laboratories will greatly enhance the integration of research and clinical practice, enabling patients to benefit more rapidly from work at the cutting edge of cardiovascular research.

Headed by eminent Professor of Cardiovascular Medicine, Anna Dominiczak, this major development has the potential to enhance Glasgow's position at the hub of the molecular genetics revolution which is currently transforming medicine and therapeutics.

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First published: 19 January 2006

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