Genetic lineage makes people react differently to drugs

Family issues: Human beings are all related, but react differently to drugs, said Prof Raj Ramesar (right), seen here with DVC Prof Danie Visser.

Genetically speaking, all human beings on the planet are 99% related to one another, but all have different predispositions to disease, and different groups of people may respond differently to therapeutic drugs.

This was emphasised recently by Professor Raj Ramesar (head of the Division of Human Genetics at UCT) at a public lecture, Exploring Ancient History Using DNA. The lecture formed part of Celebrating Africa, a partnership between UCT and Iziko Museum.

Despite the close relationships between humans, there are remarkable genetic differences between, say, Chinese and Japanese, or between Caucasians and indigenous African populations, even though all human beings originated from Central or East Africa. Despite its importance in health care, there is little data available on the differences in how indigenous Africans process drugs biologically. This is particularly relevant when one takes into account that most clinically applicable drugs have been designed and trialled elsewhere, and on other populations.

Also relevant to how well people respond to drugs is the understanding that the primary causes of a disease may be different between different individuals, families and ethnic lineages.

"This is a good reason why we should be doing research to understand why disorders to which we are predisposed are different from disorders [people are] predisposed to elsewhere in the world," Ramesar explained.

A Southern African study is being conducted in which genetic analysis is being done on individuals from the Xhosa, Zulu, and Sotho/Tswana populations, as well as the San and Herero populations from Namibia. The intention is to understand the phylogeny (evolutionary line) and the genomic structure of each of these indigenous populations. "This attempt to understand the genetic structure of our populations is extremely important when we want to understand how these may differ between individuals who are affected by a disease, and those who are not."

Understandably, this will also be applicable in understanding response to drugs, and even in designing the next generation of drugs that will be much more accurately targeted at the disease mechanism - and also tuned to an individual's (drug) metabolic capacity - than those being used currently.

In the study, researchers will look at the burden of disease in Africa, the drugs used to treat these diseases, and the genetic variations known to affect drug metabolism.

"Knowing what the variations are in those genes, it makes sense that in this population group there is a slight difference in how individuals react to certain drugs compared to those in other populations."