Doctors have long known that people differ in the way their bodies respond to a given drug. The same medicine in the same dose may work wonders in one patient but do nothing for the next.
Now an international team of researchers has traced some of these differences to a genetic defect that turns out to be one of the most widespread hereditary disorders known. Between 35 percent and 43 percent of white people carry one of the two genes needed to suffer from the defect, and from 5 percent to 10 percent have both. Figures for blacks have not been obtained.
Reporting in last week's Nature, the research team's leader, Frank J. Gonzalez of the National Cancer Institute, said the defect involves an enzyme called cytochrome p450. It is well known that cells make this enzyme to protect themselves against toxic chemicals. Enzyme p450 chemically modifies a wide range of toxins into a form that is harmless.
Cells also process drugs as foreign substances that could be toxic. As it happens, the medically useful form of some drugs is not the form in which it is taken but the form into which p450 modifies it. Thus, people who have faulty p450 enzymes will be unable to convert their medicine into its useful form.
Whether a person has the proper form of p450 depends on the genes in each cell. The genes determine the structure of the enzyme that will be manufactured within the cell.
As is the case with most genes, every cell carries two versions, one inherited from each parent. If one gene is defective and leads to the manufacture of a useless form of p450, the person may still be fine because the other copy of the gene is good. The good gene in this case is said to be dominant and the bad gene recessive. The person suffers only if both p450 genes are bad, because there is no good gene to make the proper enzyme.
Gonzalez and his colleagues said people who have at least one good gene for p450 can metabolize some drugs, such as the medicine for high blood pressure called debrisoquine, up to 200 times more efficiently than those who lack a good p450 gene but take the same dose.