Mapping heart disease markers

The arrival of tailor-made drugs that take into account a person's genetic susceptibility to some of life's most threatening …

The arrival of tailor-made drugs that take into account a person's genetic susceptibility to some of life's most threatening conditions such as heart disease, depression and cancer is likely to rank among the most significant medical treatment advances early in the new millennium.

The formation of an alliance between the Royal College of Surgeons in Ireland and France's biotechnology leader Genset means a research capability has been put in place to evaluate fully how genes influence heart disease, and make some more susceptible than others. Equally, it will find out how heart disease drugs act; why they are not efficient in some instances and their role when side-effects occur. Its main research facility will be at the RCSI in Dublin, where a joint company, Surgen, has opened a £1 million laboratory.

It is becoming increasingly obvious that a person's genome - or genetic make-up - can have a critical bearing on the life cycle of a drug. Genset evaluates this information - it is a new science known as genomics - to understand more fully a disease pathway, in turn leading to better, safer and more efficient drugs.

We are made up of about 100,000 genes, but each will exist in different forms known as alleles or variants. If a given gene is examined in different individuals, by the process of gene "sequencing", there will be some variations known as polymorphisms. Although most of these polymorphisms do not affect gene function, some will cause disease or cause an individual to be more predisposed to a disease.

READ MORE

Genset's ability to identify large numbers of polymorphisms associated with common diseases and drug responses makes it a leader in the genomics business. The RCSI's expertise in conducting large-scale clinical trials complements this. Through Surgen, it will be possible to do studies involving 20,000 patients at a time.

Central to Genset's technology is its "unique biallelic marker map". It allows scientists to home in quickly on a gene they are looking for by identifying genetic material described as biallelic markers.

Blood and DNA samples will be collected, analysed and banked by Surgen. Genset will then apply its technology to discover the various genes involved in cardiovascular disease. At this point, pharmaceutical companies are likely to come on board with a view to improving drug treatments.

Surgen's clinical director, Prof Desmond Fitzgerald of the RCSI department of clinical pharmacology, says the beauty of the map is the huge scale of genetic investigation it facilitates compared to cumbersome studies of familial links with disease which were invariably done in the past.

Genset has developed a system of finding one's way around the human genome. Not only is it accurate but its technologies allow it to identify huge amounts of genetic information in the form of genotypes, up to 200,000 genotypes per day, Genset's chief executive, Mr Pascal Brandys, predicts.

It is becoming possible for the first time to analyse the multiple genetic variants implicated in a highly complex interaction of pathways which leads to various forms of cardiovascular disease.

A combination of environmental factors and the presence of significant numbers of "low penetrance alleles" is associated with most forms of heart disease while a low penetrance allele will cause an individual to be predisposed to such a disease but not necessarily manifest it. So the only way to discover these genetic variants in unrelated individuals is by studying studying genomes of unrelated individuals.

Genset's marker map makes this possible through the work of Surgen. It is likely in time to contribute to reducing significantly the one in three death rate due to heart disease in Ireland every year.