Genetic and Genomic Considerations in Pharmacotherapeutics Vocabulary

Essential vocabulary terms, enzymes, gene variants, and regulatory concepts from Chapter 7: Genetic and Genomic Considerations in Pharmacotherapeutics.

Biomarker

A measurable substance that, when present in an organism, indicates the presence of a specific phenomenon.

Genetics

The examination of passing genetic traits from one generation to another through human genes, as well as the study of the effects of genes through the creation of specific proteins.

Genomics

The study of all of a person's genes (the genome), as well as how genes interact with each other and the environment.

Pharmacogenomics

The study of how genes affect a person's response to drugs, combining genomics and pharmacology to provide individualized, targeted, safe drug therapies.

Precision Medicine

A general approach to finding effective strategies for treatment of similar groups of patients with specific genetic, lifestyle, and environmental factors.

Endoxifen

The active form of tamoxifen (Soltamox) created via CYP2D6 metabolism, required to adequately protect against breast cancer recurrence.

CYP2C19*2

A variant form of the CYP2C19 enzyme produced by about 25\text{\null}\% of patients, resulting in a weak antiplatelet response to clopidogrel (Plavix) and an increased risk of cardiovascular events.

N-acetyltransferase-2

The enzyme responsible for metabolizing the tuberculosis drug isoniazid, existing in two genetically determined forms that cause people to metabolize the drug either slowly or rapidly.

Thiopurine methyltransferase (TPMT)

An enzyme responsible for the metabolic inactivation of thiopurine anticancer drugs (thioguanine and mercaptopurine); deficiency in this enzyme can lead to fatal bone marrow damage.

Dihydropyrimidine dehydrogenase

An enzyme that metabolizes the cancer drug fluorouracil; inherited deficiency in this enzyme can lead to toxic accumulation and severe central nervous system injury.

ADRB1

The gene coding for the $\beta_1$-adrenergic receptor, variants of which produce hyperresponsive receptors that cause exaggerated blood pressure responses to $\beta$-agonists and $\beta$-antagonists.

VKORC1

Vitamin K epoxide reductase complex 1, a multiprotein enzyme complex inhibited by warfarin; variant forms are easily inhibited and require lower warfarin doses.

HER2

Human epidermal growth factor receptor type 2, a tumor hormone receptor overexpressed in about 25\text{\null}\% of breast cancer patients that must be present for trastuzumab (Herceptin) to be effective.

EGFR

Epidermal growth factor receptor, a tumor marker whose expression on metastatic colorectal cancer cells is required for cetuximab (Erbitux) treatment.

CCR5 tropism

A property of specific HIV strains that utilize chemokine receptor 5 for cell entry, making the infection susceptible to treatment with maraviroc (Selzentry).

HLA-B*1502

A human leukocyte antigen gene variant common in patients of Asian descent that greatly increases the risk of life-threatening skin reactions when taking carbamazepine (Tegretol).

HLA-B*5701

A human leukocyte antigen gene variant that increases the risk for fatal hypersensitivity reactions in patients treated with the HIV drug abacavir (Ziagen).

Genetic Information Nondiscrimination Act (GINA)

A 2008 law providing patient protection against discrimination by employers and health insurance providers based on genetic information.

Clinical Pharmacogenetics Implementation Consortium (CPIC)

An organization that provides practice guidelines to assist healthcare providers in utilizing genetic testing to optimize drug therapy.