Pharmacogenetics: What is it?

Pharmacogenetics is a relatively new field of genetics that began to expand in the first half of the 2000s. This fact is reflected in the increasing number of articles published each year that include the words “Pharmacogenetics” or “Pharmacogenomics” in their titles. To explain pharmacogenetics in detail, it is necessary to introduce two basic concepts of genetics: genes and genetic variants.

Human DNA contains approximately 20,000 genes that make up our instruction book. These instructions are composed of a four-letter alphabet: “A,” “T,” “C,” and “G,” whose purpose is to make proteins responsible for the different functions of each of our body’s cells. Sometimes the meaning of these instructions can change due to a change, addition, or deletion of a letter, which can result in a protein with altered or deficient functions. These errors are called genetic variants or mutations, and each of us has a distinct combination of these variants that makes us unique and defines genetic variation between individuals.

Genetic variants can occur in proteins responsible for metabolizing some medications, which can lead to changes in how these medications are absorbed by the body, how they are metabolized, or in the time required for them to take effect. Sometimes, these changes can generate a protein incapable of metabolizing the medication, which can produce severe adverse effects and compromise a person’s health and, sometimes, their life. This is where the role of pharmacogenetics is fundamental, as its main objective is to study the relationship between changes that can occur in genes and the response to certain medications. These associations can play an important role in determining how a type of medication is used, from adjusting the dose to even avoiding its use. Therefore, the success of a therapy may depend on the prior performance of a pharmacogenetic study.

To contextualize the importance of pharmacogenetics, in Spain, 45% of the total population reports having taken some type of medication in the last two weeks prior to the time of the survey conducted by the INE (National Institute of Statistics). This figure doubles in people over 75 years of age. With this data in mind, we at the ADN Institut laboratory have worked to develop the most comprehensive pharmacogenetic test possible, analyzing information on genetic variants in 16 genes associated with the metabolism of more than 60 different medications, including many commonly used ones, such as ibuprofen and omeprazole, among others. The information included in our test is based on the most rigorous levels of scientific evidence according to the PharmGKB database. The levels of evidence are an indicator of how well-founded the association of certain genetic variants with the response to a type of medication is. There are four levels of evidence in total, where, briefly, levels 1 and 2 comprise those gene-drug associations that meet at least one of the following requirements:

• There are clinical guidelines with specific dose recommendations for a given genetic variant.
• There is an FDA ( Food and Drug Administration) approved annotation of the drug and genetic variant.
• There is at least one scientific publication that supports dosage recommendations according to the type of genetic variant.
• The associations of genetic variants and drug response are supported by at least two independent scientific publications.

For levels 3 and 4, there is an association between the variants and their effect on drug metabolism, but either there are insufficient scientific publications to support this association, or this association is supported by very preliminary experiments, or finally, there are several publications that question the association. The annotations in these last two levels are the most numerous, and over time and with the increase in the number of studies in this field, some will move to levels 1 or 2.

What benefits can a pharmacogenetic test bring me?

As we mentioned earlier, our genetics can determine how we respond to a medication, and each of our genetics is different. Therefore, the use of a medication cannot be generalized, especially when its use can mean the difference between curing or worsening a condition or pathology. Therefore, a pharmacogenetic test can give you the advantage of receiving a personalized therapy tailored to your genetics, increasing the likelihood of success and minimizing adverse effects.

Although the application of pharmacogenetics in clinical practice is still relatively new, there are cases where its use has been highly relevant. For example, the use of mercaptopurine in patients with acute lymphoblastic leukemia, which primarily affects children. Mercaptopurine is a drug used as an anticancer agent in chemotherapy treatments. This molecule is metabolized by a protein known as TPMT. TPMT’s action prevents the accumulation of mercaptopurine in the bloodstream, which could lead to a severe weakening of the immune system, known as myelosuppression. Myelosuppression, in turn, can cause anemia, infection-like symptoms, or thrombocytopenia, and can be fatal. The presence of genetic variants can compromise the function of the TPMT protein and, consequently, increase the risk of mercaptopurine accumulating in the bloodstream. Currently, in the United Kingdom, 67% of physicians prescribing mercaptopurine request testing for variants in the TPMT gene before administering it, avoiding potentially fatal consequences from using the treatment.

What is the future of pharmacogenetics?

As new scientific studies are conducted on pharmacogenetics, a greater number of drugs and genetic variants will be associated, allowing for optimal medication use. The AboutMe Pharmacogenetics test is available so your doctor can provide you with personalized guidelines on the use of certain medications. This way, you’ll take full advantage of current knowledge about the interaction of your genetics with certain drugs and thus access a revolutionary new medicine where genetics meets clinical practice to determine the best therapy for your individual needs. This test is performed using a simple saliva sample, with the convenience of managing the entire process online by requesting a sample extraction kit that the ADN Institut laboratory sends and collects free of charge. Genetic information is no longer inaccessible to most people; now, it comes to your home.

Do you have any questions?