How do genes affect our responses to medicines?
Differences in our genes can affect the way in which we respond to medicines in two ways:
1. Variation in the way the body processes a medicine
Variation in DNA can lead to altered activity of enzymes that are responsible for the absorption, metabolism and excretion of medicines. If a medicine is broken down too quickly it may not be effective. Alternatively, slow metabolism can lead to the build-up of toxic levels of a medicine. Even a single change in the DNA can affect the way the body processes a medicine.
An enzyme in the liver, CYP2D6, is involved in the metabolism of nearly one quarter of medicines, including anti-depressants and beta-blockers used to treat heart disease. Variations in the CYP2D6 gene may alter the activity of this enzyme. People with reduced levels are unable to process some medicines properly. In some cases the medicine will not be effective; in other cases patients will suffer serious side effects. For example, the painkiller codeine has no effect on approximately 7% of Caucasians because of a CYP2D6 variant. There is currently no routine pharmacogenetic testing for CYP2D6; but a diagnostic chip that will test for a large number of 2D6 variants will be introduced in 2003.
2. Variation in the genetic characteristics of a disease
Many diseases that are currently diagnosed as a single clinical condition may actually have a number of underlying causes, based on different genetic characteristics. Understanding more about the genetic basis of disease may provide information about what medicine would be effective. Some cells, for example those in cancerous tumours, have an altered genetic make-up. This change only occurs in the cancer cells, and not in normal tissue, and may influence treatments.
A particularly aggressive form of breast cancer is associated with a genetic variation which leads to overproduction of a protein called HER2. Patients with breast cancer can be tested to find out if they have high levels of HER2. If they do, the medicine Herceptin (trastuzumab) is given to treat this specific type of cancer.
There are a number of factors that affect our response to medicines, including age, sex, interaction with other medicines, and diet. A genetic variant alone will rarely provide a precise prediction of the response of a particular patient.