The emerging field of pharmacogenomics involves the study of human genetic differences that contribute to differences in reactions to drugs. In some cases, such as malignant hyperthermia, the variability may take the form of an iatrogenic, or drug-induced, illness. In other cases, there may be a difference in response to the drug, as has been seen in the cases of some asthma sufferers who do not respond to an asthma medication because they have a mutation that changes the receptor protein that binds the drug. One form of glaucoma results when individuals who are susceptible to the effects of corticosteroids are exposed to dexamethasone, which causes elevated intraocular pressure that will lead to glaucoma if left untreated (see Figure 24.1). In addition, some patients do not respond to one or more of the glaucoma medications they are given, possibly because of genetic differences in the body's ability to react to the drug. Often, the real array of variability in response to a drug is expected to be complex and involve differences in many different genes in the human genome. Thus, for example, we might expect the efficacy of a drug to be affected not only by the sequence of the proteins that the drug will interact with in the human body but also by differences that affect proteins that will transport the drug into the cell, degrade and eliminate the drug, pump the drug out of the cell, target the drug to a particular place in the body, or carry out an immune reaction to the drug. Eventually, it is hoped that it will be possible to carry out genetic tests that will tell us whether one drug will work better than another for a particular person, or what side effects or risks there would be for that person if they take the drug.
trait will only be manifested by people who have been exposed to the food or allergen. A trait called favism is characterized by a form of hemolytic anemia that happens after consumption of fava beans. Someone who has never consumed fava beans would not know whether they would be susceptible to favism or not. The genetics of lactase persistence/lactose intolerance, discussed in Chapter 17, is very hard to evaluate in countries where dairy products are not part of the diet. Sorting out the genetic components of allergies can be especially difficult because often people with allergies react to many different allergens, not just one, while being exposed to a vastly larger array of potential allergenic culprits. However, in some cases, such as penicillin allergy, the eliciting event (taking the antibiotic) and the unusual nature of the allergic reaction (a rash) make it easier to identify than some more generalized allergies to airborne allergens.
In a world in which many things start going wrong with people as they age, we need to think of aging as one of the eliciting events for conditional traits. Age-dependent penetrance is the term used to express the increased expression of a trait in older populations when compared with younger populations. Issues of aging and conditional expression of traits are genetically complex. This becomes complicated as we consider that genetic variation affects the rate at which we age, which in turn affects the rate at which aging causes us to express other traits caused by genetically variable susceptibilities.
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