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Pharmacogenomics (sometimes called pharmacogenetics)
is a field of research focused on understanding how
genes affect individual responses to medications.
The long-term goal of pharmacogenomics is to help
doctors select the drugs and dosages best suited for
each person. Just as our genes determine our hair
and eye color, they are partially responsible for
how our bodies respond to medications.
Genes are instructions, written in DNA, for building
protein molecules. Different people can have
different versions—slightly different DNA
sequences—of the same gene. Some of these variations
are common and some are rare. Some are relevant for
health, such as those associated with a tendency to
develop certain diseases.
Pharmacogenomics looks at variations in genes for
proteins that influence drug responses. Such
proteins include a number of liver enzymes that
convert medications into their active or inactive
forms. Even small differences in the genetic
sequences of these enzymes can have a big impact on
a drug’s safety or effectiveness.
One example involves a liver enzyme known as CYP2D6.
This enzyme acts on a quarter of all prescription
drugs, including the painkiller codeine, which it
converts into the drug’s active form, morphine.
The CYP2D6 gene exists in more than 160 different
versions, many of which vary by only a single
difference in their DNA sequence, although some have
larger changes. The majority of these variants don’t
affect drug responses.
Some people have hundreds or even thousands of
copies of the CYP2D6 gene (typically, people have
two copies of each gene). Those with extra copies of
this gene manufacture an overabundance of CYP2D6
enzyme molecules and metabolize the drug very
rapidly. As a result, codeine may be converted to
morphine so quickly and completely that a standard
dose of the drug can be an overdose.
On the other end of the spectrum, some variants of
CYP2D6 result in a nonfunctional enzyme. People with
these variants metabolize codeine slowly, if at all,
so they might not experience much pain relief. For
these people, doctors might prescribe a different
type of pain reliever.
The Food and Drug Administration, which monitors the
safety of all drugs in the United States, has
included pharmacogenomic information on the labels
of more than 150 medications. This information —
which can cover dosage guidance, possible side
effects or differences in effectiveness for people
with certain genomic variations — can help doctors
tailor their drug prescriptions for individual
patients.
Pharmaceutical companies are beginning to use
pharmacogenomic knowledge to develop and market
drugs for people with specific genetic profiles.
Studying a drug only in those likely to benefit from
it could speed up and streamline its development and
maximize its therapeutic benefit.
Additionally, if scientists can identify the genetic
basis for certain serious side effects, drugs could
be prescribed only to people who are not at risk for
them. As a result, potentially lifesaving
medications, which otherwise might be taken off the
market because they pose a risk for some people,
could still be available to those who could benefit
from them.
Currently, doctors base the majority of their drug
prescriptions on clinical factors, such as a
patient’s age, weight, sex, and liver and kidney
function. For a small subset of drugs, researchers
have identified genetic variations that influence
how people respond. In these cases, doctors can use
the pharmacogenomic information to select the best
medication and identify people who need an unusually
high or low dose.
For more information
National Institute of General Medical Sciences
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