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Pharmacogenetics

e05da56683668cf1eb5cc11046232fa2Pharmacogenetics is the study of inherited genetic differences in drug metabolic pathways (and other pharmacological principles, like enzymes, messengers and receptors) which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects. The term pharmacogenetics is often used interchangeably with the term pharmacogenomics which also investigates the role of acquired and inherited genetic differences in relation to drug response and drug behaviour through a systematic examination of genes, gene products, and inter- and intra-individual variation in gene expression and function.

Available pharmacogenetics tests in our laboratory

  • Antiplatelet therapy sensitivity [Clopidogrel (Plavix)]
  • Anticoagulation therapy sensitivity (Warfarin, Acenocoumarol)
  • Statins sensitivity (atorvastatin, rosuvastatin, simvastatin)
  • Proton pump inhibitors sensitivity (Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole)
  • Antidepressants sensitivity
  • Chemotherapy sensitivity (cisplatin, capecitabine, tamoxifen)
  • NGS for a comprehensive pharmacogenetics test

Learn more about pharmacogenetics:

What is pharmacogenetics and what is pharmacogenomics?

Pharmacogenetics is a new scientific inter-discipline that has from recently been integrated in everyday medical practice and focuses on the individual response of each patient in the treatment of various drugs. Pharmacogenetics tests reflect individual relevant differences by testing variations in genes encoding enzymes that metabolize the drugs.

In oncology, pharmacogenetics is the study of germline mutations (e.g., single-nucleotide polymorphisms affecting genes coding for liver enzymes responsible for drug deposition and pharmacokinetics), whereas pharmacogenomics refers to somatic mutations in tumoral DNA leading to alteration in drug response (e.g., KRAS mutations in patients treated with anti-Her1 biologics). Pharmacogenetics is believed to account for inter-ethnic differences (e.g., between patients of Asian, Caucasian and African descent) in adverse events and efficacy profiles of many widely used drugs in cancer chemotherapy.

Pharmacogenetic tests are a new form of predictive genetic tests that may see increased clinical application. These tests predict a person’s individualized response to a drug or class of drugs (efficacy and side effects) by testing for gene variants such as those that code for drug-metabolizing enzymes. These tests offer a means to reduce adverse reactions and proper dosing. When clinicians know the gene variant is present, they can adjust the dose. These tests can help to choose the right therapy for people who need longer treatment times.

Why do pharmacogenetics tests need to be an integral part of the therapy prescription?

When formulating therapy for a particular disease, doctors usually choose one drug from several analogous drugs. The dose and time of taking the medicine are always determined according to the average metabolic rate of the drug. A standard dose is prescribed for all patients, based on factors such as age, weight, and gender.

However, from a clinical point of view, each individual responds differently and uniquely to the particular therapy. Thus, pharmacogenetics offers the possibility for individualizing drug therapy based on the patient’s authentic genetic constitution. Scientific studies implicate that the integration of the genetic factor while prescribing the drug before initiating with therapy is a key element in increasing the efficacy of the drug on the one hand, and reducing the likelihood of adverse side effects on the other.

What is the purpose of the pharmacogenetics tests?

  • To determine if the particular medication is an effective and an appropriate therapy or whether it may be more convenient to be treated with another drug
  • To determine the most appropriate dose of the particular drug and to optimize it
  • To determine whether receiving the particular drug would have adverse and negative consequences and subsequently reduce them (for example in statins and chemotherapy)

Who needs pharmacogenetics tests the most?

These tests are useful and necessary for all people who take a particular medicine, but we especially recommend them to:

  • people who need longer treatment with certain drugs
  • people who themselves noticed negative consequences after taking a particular drug
  • people in whom a certain drug previously had no side effects, but suddenly it began to cause adverse consequences
  • people that are treated with chemotherapy (for example cisplatin or capecitabine)

Clopidogrel (Plavix) sensitivity

What is CLOPIDOGREL (PLAVIX) and why is the pharmacogenetics test for it very important?
CLOPIDOGREL BISULFATE is an antiplatelet drug known under the commercial name PLAVIX (or ANGICLOD, CARDOGREL, KLOGAN-SANOVEL, KLOPIDEX, KLOPIDOGREL AKTIV, SYNETRA, VATOUD, ZYLLT, etc.), and it is used to prevent platelet aggregations in the coronary, peripheral and cerebrovascular arteries – aggregations that if not treated can result in a heart attack or in a stroke in high-risk patients.

Which conditions are treated with anti-platelet therapy?

  • Acute coronary syndrome
  • Infarction
  • Peripheral vascular conditions (weak capillary circulation in the lower limbs)
  • Percutaneous coronary intervention (angioplasty, coronary stents, coronary artery bypass)

Is there a risk of side effects from CLOPIDOGREL therapy?
Despite the widespread use of CLOPIDOGREL, recent studies show that in 25% of patients taking this anti-platelet therapy exhibit certain drug-resistance that is genetically determined, which means that the drug does is not metabolized appropriately in some people. By taking inappropriate treatment, patients have an increased risk of adverse events such as infarction, effusion, and death. Additionally, according to studies conducted at our clinic, the risk of clogging in patients with an implanted stent increases 8 times if they take a drug that does not suit their genetic constitution.

What can be done?
CLOPIDOGREL is a pro-drug; after its administration into the body, it is converted from inactive to active form in the liver. Several enzymes are involved in this process, of which the most significant is the cytochrome P450 2C19 – CYP2C19. Mutations in the gene encoding the enzyme CYP2C19 are associated with slower/faster metabolism of the drug.
Depending on the presence or absence of these mutations in the patient, normal dosage of CLOPIDOGREL or the usage of another anti-platelet therapy is recommended. Consequently, there are international guidelines which indicate that it is necessary and mandatory to do a pharmacogenetics analysis for each CLOPIDOGREL user.

In addition to all of this, we emphasize that pharmacogenetics testing for the sensitivity of clopidogrel is of great importance and we encourage all patents who take the drug to do the test.

Method: Quantitative PCR is used to detect mutations in the CYP2C19 gene which is involved in the metabolism of clopidogrel.

Sample: Blood

Statin sensitivity

What is a STATIN and why is the pharmacogenetics test for statins important?
STATINS (ATORIS, COUPET, EPRI, HOLLESTA, ROPUIDO, ROSWERA, TORVEX, etc.) are a group of drugs that can help reduce LDL cholesterol levels by blocking the cholesterol synthesis in the liver and by inhibiting the enzyme HMG-CoA reductase. LDL cholesterol is often termed “bad cholesterol” because its high blood concentrations can lead to the development of many other health-related diseases, such as:

  • coronary heart disease – when blood supply to the heart becomes limited
  • angina – severe chest pain caused by coronary heart disease
  • heart attack – when blood supply to the heart is blocked
  • stroke – when blood supply to the brain is blocked

Statin therapy can cause many side effects. Myopathy is one of the most common side effects of statin therapy. It can affect 10-25% of all patients treated with statins. Side effects that arise in statin therapy include the following: myopathy, myalgia, myonecrosis, and rhabdomyolysis (in 0.1% of patients, which even imposes the need for hospitalization). At the onset of myopathy caused by statin therapy there is an increase in the concentration of the enzyme creatine kinase, there is evidence of kidney damage or certain muscle symptoms with no muscle injury present.

In our laboratory, we analyze genetic variations in the SLCOB1 gene that can provide us with information as to whether each individual patient has an increased risk of side-effects caused by statin therapy. Then, doctors use this information for individual adjustment of the therapy of each individual patient (dose optimization or a prescription for a different therapy).

Method: Quantitative PCR is used to detect mutations in the SLCO1B1 which is involved in the metabolism of statins.

Sample: Blood