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Genes alter responses to drugs because the genes influence many parts of the body iteself. One of the
In the case of gender responses to antidepressants, women show greater response to serotonin specific anti-depressants because women naturally have lower levels of serotonin than men do. This makes women more likely to develop a type of depression marked by low serotonin levels, but it also means that women will respond better to replacement of serotonin.
Because people of the same race carry similar genes, studies based on race were the earliest types of pharmacogenetic studies. One study evaluated the levels of alcohol dehydrogenase in people of different nationalities. This is an enzyme involved in the metabolism of alcohol. When people with high levels of this enzyme, or people in whom the enzyme acts more rapidly than in other people, drink alcohol, they are subject to facial flushing and slowing of the heartbeat. The activity of this enzyme is determined by genetics, and different levels can be seen in different races because these people belong to the same gene pools. Among Asiatic people, 85% have high levels of this enzyme, compared to 20% of Swiss people, and only 5–10% of British people.
Another trait that is influenced by genes is a liver enzyme, CYP2D6. This enzyme metabolizes some drugs by converting them to a form that can be removed from the body. Genes determine the level of this enzyme in the liver. People with low levels of CYP2D6 will metabolize drugs slowly. Slow metabolism means the drugs will act for a longer peiod of time. Slow metabolizers reaspond to smaller doses of medications that are eliminated by this enzyme, while fast metabolizers, people who have a lot of the enzyme, will need larger drug doses to get the same effects. At the same time, low levels of CYP2D6 means that people taking the drugs that are metabolized by this enzyme will have higher drug levels, and are more likely to have unwanted side effects.
Another enzyme that can be important in drug dosing is called 2C9, and this enzyme is responsible for metabolizing the anticoagulant drug warfarin (Coumadin). Most people take warfarin in a dose of about 5 milligrams a day, but people who have low levels of 2C9 normally require a dose of only 1-5 milligrams a week.
Yet another mechanism of drug activity is the presence or absence of a specific drug receptor sites. Drugs act by binding to specific chemicals, receptor sites, within body cells. Genes may help determine how many of these cells there are. The action of the widely used antipsychotic drug haloperidol (Haldol) depends on its ability to bind to the dopamine (D2) receptor site. The number of these sites are determined by genetics. In one study, 63% of patients whose genes caused a large number of these receptor sites had a response to treatment with haloperidol, while only about 29% of patients with a smaller number of dopamine (D2) receptor sites did well on the drug.
Other genetic studies indicate that genes may affect how people respond to foods as well as to drugs. An Australian study of osteoporosis (softening of the bones that often occurs in elderly people) reported that separate genes may affect response to vitamin D, calcium, and estrogens.
Author Info: Sam Uretsky, The Gale Group Inc., Gale, Detroit, Gale Encyclopedia of Medicine, 2002
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