Pharmacogenetics and Cardiovascular Disease
Pharmacogenetics and Cardiovascular Disease
The genetic polymorphisms that may affect individual responses to cardiovascular agents are reviewed, and the application of pharmacogenetics to cardiovascular disease management is discussed.
Pharmacogenetics is the search for genetic polymorphisms that affect responses to drug therapy. Investigators have found many associations between genetic polymorphisms and responses to cardiovascular drugs. Some of these relationships have been demonstrated in large patient populations, such as patients with ischemic heart disease receiving statins. Study data consistently show a greater response to statins in ischemic heart disease patients with genotypes associated with worse prognoses. Studies of other polymorphisms, such as those in the genes encoding angiotensinconverting enzyme and
1-adrenergic receptors, have less consistently found relationships between these variations and cardiovascular drug responses. For gene drug response associations for which the data are inconsistent, the interaction of multiple polymorphisms in multiple genes coding for proteins affected by drug therapy or influencing drug metabolism may prove to have a greater influence on drug responses than any one polymorphism. Once the polymorphisms that best determine the response to a particular drug are known and tests to rapidly identify these variations are available, individual patients may be screened for genetic polymorphisms before drug therapy is begun and the information used to choose agents with the greatest potential for efficacy and least potential for toxicity.
Pharmacogenetics has many possible applications in the drug therapy of cardiovascular diseases. Much more must be learned, however, before pharmacogenetic factors can be routinely incorporated into therapeutic decisions.
Factors that may be taken into account when selecting drug therapy for a patient with cardiovascular disease include age, race, concomitant diseases, medications, and renal and hepatic function. In addition, abundant data from large clinical trials and consensus guidelines from expert panels are available to help steer cardiovascular drug therapy decisions. However, despite careful selection of drug therapy on the basis of these factors, clinical trial data, and guidelines, there is no guarantee that a given treatment will be effective or well tolerated in a given patient. This is particularly the case with nonwhite patients, who are traditionally underrepresented in clinical trial populations in cardiology.
Pharmacogenetics and pharmacogenomics involve the search for genetic polymorphisms that influence responses to drug therapy. These disciplines offer the opportunity to provide individualized drug therapy on the basis of a person's genetic makeup, thus increasing the likelihood of achieving treatment goals and limiting adverse effects from drug therapy. Pharmacogenetics generally refers to the study of variations in a single gene, whereas pharmacogenomics is the study of variations in multiple genes. For example, a study examining a polymorphism in the gene coding for cytochrome P-450 (CYP) isoenzyme 2C9 that affects the response to warfarin would be a pharmacogenetic study, and a study of polymorphisms in the genes coding for CYP2C9, antithrombin III, and factor VII affecting the warfarin response would be a pharmacogenomic study.
This article discusses the genetic polymorphisms that may affect individual responses to various classes of cardiovascular agents and how pharmacogenetics and pharmacogenomics may be applied to cardiovascular disease management. For convenience and because most examples discussed in this article involve single genetic variations, "pharmacogenetics" will be the predominant term used.
The genetic polymorphisms that may affect individual responses to cardiovascular agents are reviewed, and the application of pharmacogenetics to cardiovascular disease management is discussed.
Pharmacogenetics is the search for genetic polymorphisms that affect responses to drug therapy. Investigators have found many associations between genetic polymorphisms and responses to cardiovascular drugs. Some of these relationships have been demonstrated in large patient populations, such as patients with ischemic heart disease receiving statins. Study data consistently show a greater response to statins in ischemic heart disease patients with genotypes associated with worse prognoses. Studies of other polymorphisms, such as those in the genes encoding angiotensinconverting enzyme and
1-adrenergic receptors, have less consistently found relationships between these variations and cardiovascular drug responses. For gene drug response associations for which the data are inconsistent, the interaction of multiple polymorphisms in multiple genes coding for proteins affected by drug therapy or influencing drug metabolism may prove to have a greater influence on drug responses than any one polymorphism. Once the polymorphisms that best determine the response to a particular drug are known and tests to rapidly identify these variations are available, individual patients may be screened for genetic polymorphisms before drug therapy is begun and the information used to choose agents with the greatest potential for efficacy and least potential for toxicity.
Pharmacogenetics has many possible applications in the drug therapy of cardiovascular diseases. Much more must be learned, however, before pharmacogenetic factors can be routinely incorporated into therapeutic decisions.
Factors that may be taken into account when selecting drug therapy for a patient with cardiovascular disease include age, race, concomitant diseases, medications, and renal and hepatic function. In addition, abundant data from large clinical trials and consensus guidelines from expert panels are available to help steer cardiovascular drug therapy decisions. However, despite careful selection of drug therapy on the basis of these factors, clinical trial data, and guidelines, there is no guarantee that a given treatment will be effective or well tolerated in a given patient. This is particularly the case with nonwhite patients, who are traditionally underrepresented in clinical trial populations in cardiology.
Pharmacogenetics and pharmacogenomics involve the search for genetic polymorphisms that influence responses to drug therapy. These disciplines offer the opportunity to provide individualized drug therapy on the basis of a person's genetic makeup, thus increasing the likelihood of achieving treatment goals and limiting adverse effects from drug therapy. Pharmacogenetics generally refers to the study of variations in a single gene, whereas pharmacogenomics is the study of variations in multiple genes. For example, a study examining a polymorphism in the gene coding for cytochrome P-450 (CYP) isoenzyme 2C9 that affects the response to warfarin would be a pharmacogenetic study, and a study of polymorphisms in the genes coding for CYP2C9, antithrombin III, and factor VII affecting the warfarin response would be a pharmacogenomic study.
This article discusses the genetic polymorphisms that may affect individual responses to various classes of cardiovascular agents and how pharmacogenetics and pharmacogenomics may be applied to cardiovascular disease management. For convenience and because most examples discussed in this article involve single genetic variations, "pharmacogenetics" will be the predominant term used.
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