Pharmacogenetics Tests
PHARMACOGENETICS IN CARDIOLOGY
Individual variability in drug response is a major cause of therapeutic failure and drug induced adverse reactions.
With pharmacogenetic analysis, the genes that regulate the activity, metabolism and transport of a drug can be tested for genetic polymorphisms that are responsible for the genetic variability. The individual pharmacogenetic profile allows for the most appropriate selection and correct drug dosage. Treatment becomes more effective and safe, preventing the occurrence of side effects and reducing health care costs.
Today, more than 10% of FDA approved drugs contain personalized pharmacogenetics information.
The test analyzes polymorphisms that confer variability of the enzymes that metabolize various drugs used in the treatment of cardiovascular diseases. The test detects the following alleles: CYP2D6 *1 and *4, CYP2C9 *1, *2 and *3, CYP2C19 *1, *2 and *17 genotype and VKORC1 1137C> T (see following table).
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ANTIPSYCHOTIC AND ANTIDEPRESSIVE PHARMACOGENETICS
There is a wide variability in how patients respond to drugs, the appearance of side effects and symptoms caused by drug toxicity. This variability depends on age, sex, liver and kidney function as well as genetic factors.
The use of psychotropic drugs (antidepressants and antipsychotics) is an area where the response is very variable. Though there is a wide variety of available drugs, close to half of patients do not respond to treatment as expected.
In the case of antidepressants, 30-40% of patients do not respond significantly to therapy at the beginning of treatment and 60-70% show no signs of remission.
An incomplete response to treatment leads to a longer period of therapy and a consequential increased risk of adverse effects. The characterization of the profile of response to psychotropic drugs is of great clinical and economic utility.
40-90% of patients using this type of drug manifest side effects, the prevalence and severity of which depend on genetic variations between individuals.
Most psychotropic drugs are metabolized by two cytochrome P450 enzymes, CYP2D6 and CYP2C19. Genetic alterations in the genes encoding these enzymes are responsible for the variability in response and mode of action of these drugs. The characterization of genetic variants can identify patients in whom a certain treatment is not effective and carries a higher risk of toxicity.
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TAMOXIFEN PHARMACOGENETICS
Approximately 30% of woman that undergo Tamoxifen therapy do not respond to treatment.
There is epidemiological and experimental evidence linking estrogen
in the pathogenesis of breast cancer. Studies in postmenopausal women with breast cancer revealed estrogen levels 15% higher than those who do not have this tumor.
70% of breast cancers are positive for estrogen receptors. Thus, tamoxifen, interfering with the action of this hormone, provides an effective therapy.
Tamoxifen is an anti-estrogen that inhibits the synthesis and release of cell growth factors. It is used as adjuvant therapy and prevention of breast cancer in patients with positive estrogen receptors.
30% of women undergoing treatment with tamoxifen, do not get the expected result. This drug is not effective and relapses are often observed. A major cause of resistance to tamoxifen is the presence of inactive alleles of cytochrome P450 2D6 (CYP6D6), an enzyme responsible for conversion of tamoxifen into endoxifen, the metabolite responsible for the anti-tumoral action.
This conversion is mediated by CYP2D6 that has high individual variability and dependence on other factors (environmental, other treatments and / or genetic).
The presence of certain genetic variations, leads to an inability to convert tamoxifen into endoxifen and a consequent loss of therapeutic efficacy. Patients with these variants in homozygosity are poor metabolizers and have significantly lower levels of endoxifen (25%). There are a number of drugs often prescribed along with tamoxifen, which are potent inhibitors of the CYP2D6 enzyme. The most used are serotonin-specific reuptake inhibitors (SSRIs), such that when used simultaneously, endoxifen levels decreased approximately 60%.
The alleles CYP2D6 *3, *4, *5 and *10 are associated with a decrease or even absence of enzyme activity.
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