Pharmacogenetics in cardiology

Adapting the drug to your patient’s dose

Know to prevent

This genetic study allows to identify patients in whom a certain treatment will not be effective or may have a high risk of adverse effects.

Application

The study is indicated:

In people with a different drug effect than expected
In people with a family or personal history of adverse effects to the analyzed drugs
Before starting treatment with these drugs

How is the test performed?

The study is performed on a DNA sample, obtained from peripheral blood, saliva or oral mucosa cells.

Pharmacogenetics in Cardiology

There is great variability in the way in which patients respond to medications and in the symptoms attributable to their toxicity.

The variability depends on several factors such as age, sex, liver and kidney function and also genetic factors. Pharmacogenetic studies study the genes that influence the activity, metabolism or transport of a drug, in order to identify the genetic polymorphisms that cause the variability of the effect.

The pharmacogenetic study of a patient allows the most appropriate selection of the drug and the indication of the correct dose, achieving a more effective and safe therapeutic approach, since it avoids the appearance of side effects, thus reducing the associated costs.

Pharmacogenetic information is being progressively incorporated into the development and validation protocols of new drugs and the information that accompanies many medications. At this time, more than 10% of the drugs approved by the FDA contain personalized information on pharmacogenetics.

The Genolife laboratory has specific pharmacogenetic analyzes of cardiology in the form of a panel and they are also available as individual analyzes for different drugs:

Cardiology Pharmacogenetics (complete panel)
Pharmacogenetics of Clopidogrel (Plavix®)
Pharmacogenetics of Dicumarinics (Warfarin)

What is the test based on?

The test analyzes polymorphisms that confer variability to the enzymes that metabolize various drugs used in cardiology. A large majority of these drugs are metabolized by enzymes of the Cytochrome P450 (CYP450) group. In several of these enzymes (CYP2D6, CYP2C9 and CYP2C19) polymorphisms that confer variability in enzymatic activity have been identified (See table).

The test detects the following alleles: CYP2D6 * 1 and * 4, CYP2C9 * 1, * 2 and * 3, CYP2C19 * 1, * 2 and * 17 and the genotype VKORC1 1137C> T.

Medicament	Gene	Alleles	Phenotype
CarvedilolMetoprolol (lopresor®) Propranolol Timolol	CYP2D6	4*	Slow metabolizer Diminished enzyme activity -> lower dose Alters the metabolism of several beta-blockers
Candesartan (Atacand®)Irbesartan (Aprovel®) Losartan (p) (Cozaar®) Acenocoumarol (Sintrom®) Warfarina (p-profármaco)	CYP2C9	2/3	Slow metabolizer Decreased enzyme activity → lower dose * 2 → Present in about 11 17% of the Caucasian population Responsible for the metabolization of dicoumarin anticoagulants * 3 → Present in about 610% of the Caucasian population Responsible for the metabolism of antihypertensive agents of the group of angiotensin II receptor antagonists such as losartan.
Clopidogrel(p) (Plavix®)Propranolol(p-profármaco)	CYP2C19	* 2 *17	Slow metabolizer Decreased enzyme activity → lower dose Prodrug does not pass into active form → ineffective Present in about 25% of the population Caucasian Responsible for the metabolism of beta-blockers and platelet antiaggregants Ultra-fast metabolizer Enlarged enzyme activity → higher dose Prodrug → lower dose Present in about 40% of the population Caucasian
Acenocoumarol (sintrom®)Warfarina	VKORC1	1137T	Slow metabolizer Decreased enzyme activity → lower dose This allele has a frequency of about 30 -40% in Caucasians

p-Prodroga (to active form depends on enzyme).
According to the genotype and regarding the profile we can distinguish the following groups:

Metabolizer	Effect	Dosage adjusted to the phenotype
Slow	Increased risk of Adverse effects	1 1/2 tablets
Intermediate	Adjust dose	1 tablet
Normal / Fast	Effective	2 tablets
Ultra-Fast	Ineffective	3 tablets

Important note:

This test analyzes only the variants mentioned, so the possibility of an intermediate or slow metabolizing phenotype due to other variants of these or other genes, not included in this panel, is not excluded.
The test does not replace clinical and therapeutic monitoring. In the case of dicumarinics, it does not replace the periodic control of coagulation time and INR.

Additional Information:

Ask about the molecular diagnosis of thrombophilia and pharmacogenetic study of Dicumarinics using Mutations Panel.