https://issuu.com/kenhaglindPharmacogenetics is a new field that combines the science of pharmacology with the science of the human genome, or genomics.Genetic variations alter drug responses, sometimes changing how a drug works and other times making it less effective or more likely to cause side effects.
One example is a gene variant called CYP2D6 that affects how a quarter of all prescription drugs work. This can cause people to have trouble responding to a medication, such as clopidogrel (Plavix) for antiplatelet therapy.
CYP2D6
CYP2D6 is the gene encoding a protein that helps to metabolize different drugs. It is used in pharmacogenetics to identify people who have a lower or higher sensitivity to certain types of drugs.
Among CYP2D6 variants, there are two types of phenotypes: ultra-rapid (UM) and intermediate metabolizer (IM). Individuals with the UM phenotype metabolize CYP2D6 substrates more rapidly than people with the IM phenotype, which means that they can metabolize drugs at very low plasma drug levels.
However, UM phenotypes can also lead to poor drug response and increased drug dosage requirements. In particular, this is the case with antidepressants.
Several studies show a link between CYP2D6 variants and personality traits in healthy individuals, and an association with psychiatric disorders. For example, a lower frequency of PM phenotypes was found in schizophrenia patients, and a higher frequency of UM phenotypes in subjects who died by suicide or had eating disorders with suicidal attempts.
CYP2C19
CYP2C19 is an enzyme that helps process many commonly used medications, including proton pump inhibitors (PPIs), tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Variants in the CYP2C19 gene can affect how well this enzyme works.
Some CYP2C19 variants are harmless, but others can make certain drugs less effective. For example, patients with the CYP2C19*2 variant have a reduced ability to use clopidogrel and are at higher risk of heart damage after a coronary stent procedure.There are also a number of CYP2C19 variants that can increase the risk of developing hypertriglyceridemia. Additionally, there is a link between CYP2C19 variants and depression.
23andMe Pharmacogenetics reports can help you learn if you have specific DNA variants in the CYP2C19 gene that could affect how you process certain medications. These reports can be helpful when you start a new medication and can be shared with your healthcare provider.
CYP3A4
CYP3A4 is one of the most important cytochrome P450 enzymes found in the liver and intestine. It catalyzes a variety of oxidative biotransformations and is primarily responsible for drug metabolism in these organs.
Despite the importance of CYP3A4 to drug metabolism, there is a significant level of interindividual variability in this enzyme’s activity (Wilkinson 2005). This may be the result of both genetic and environmental factors.
As a result, there is a need to understand the impact of gene mutations on CYP3A4-mediated drug metabolism. This knowledge can help identify a potential drug interaction that has the potential to alter clinical outcomes.
CYP3A4 and its homologue CYP3A5 have overlapping substrate specificities and a significant amount of data suggests that variants in either of these genes influence the pharmacokinetic properties and clinical toxicity of a large number of drugs. Therefore, a combination of genotyping tests for defective variants is necessary to fully understand the effect of CYP3A4 and CYP3A5 on the metabolic disposition of a wide range of pharmaceutical compounds.
CYP3A6
The cytochrome P450 (CYP) enzyme family is involved in metabolizing many drugs, including nearly 50% of all medications on the market. These enzymes oxidize chemicals to a water-soluble form, allowing them to be excreted by the kidney.
CYP3A6 is involved in the metabolism of pain medications and some anticancer agents, including tamoxifen. It is also important in the synthesis of other compounds, such as melaleuca oil and testosterone.
As with the other genes in this section, CYP3A6 was resequenced in the CSKT population to identify known variants at low frequencies and to discover new gene variants that may affect drug metabolism.
Variants were identified only in exonic regions of CYP3A6 and a limited proportion of intronic and untranslated regions of CYP3A4, CYP3A5, and CYP2C9.
Several variants were not detected, including alleles for CYP3A4*1B and CYP3A5*1B (Figure 1B), which have not been found in other populations. However, a linkage disequilibrium (LD) was observed between CYP3A4*1B*2 and CYP3A5*1B in the CSKT population.
