Introduction to Pharmacogenetics and Pharmacogenomics Flashcards
What is pharmacogenetics?
Study of unusual responses to drugs and other foreign compounds that have a hereditary basis
The term was first used in 1959 by Fredrich Vogel.
Who first used the term pharmacogenetics and when?
Fredrich Vogel in 1959
What are some examples of drugs with variable patient responses prior to the term pharmacogenetics?
- Isoniazid
- Primaquine
- Succinylcholine
What role do cytochrome P450 enzymes (CYPs) play in pharmacogenetics?
CYPs do 80% of phase 1 metabolism
What are the classifications of metabolizers in pharmacogenetics?
- Ultrarapid metabolizers
- Extensive metabolizers
- Poor metabolizers
- Intermediate metabolizers
What is copy number variation in genetics?
DNA segments at 1 kb or larger with a variable number of copies in comparison with a reference genome
What is pharmacogenomics?
Individualization of drug therapy using information from the human genome project
What year was the term pharmacogenomics first used?
1997
What historical observation did Pythagoras make related to pharmacogenetics?
Certain individuals suffered a serious adverse reaction to fava beans
What genetic deficiency is associated with adverse reactions to fava beans?
Variation in glucose-6-phosphate dehydrogenase (G6PDH)
What gene encodes the ability to taste phenylthiocarbamide?
TAS2R38
What significant genetic polymorphisms were identified in 1950?
- Glucose-6-phosphate dehydrogenase
- Cholinesterase
- Acetylation
What is a genetic polymorphism?
A mutation occurring at a population frequency of at least 1 in 100
What are functional polymorphisms?
They are polymorphisms that affect biological activity like:
* Amino acid substitution
* Effect on transcription factor binding
* Altered splice site
* Whole gene sequences deleted or duplicated
What are synonymous mutations?
Single nucleotide change in the coding region that does not alter the amino acid sequence
What are non-synonymous mutations?
Changes to the nucleotide sequence that alter the amino acid sequence
What are the two general mechanisms by which DNA methylation regulates gene expression?
- Methylation of gene promoters may reject binding of transcription factors
- Transcriptional silencing via changes in chromatin conformation
What is the consequence of pharmacogenetic polymorphisms?
Different responses to drugs
What is drug toxicity in pharmacogenetics?
Exaggerated response or effect on inappropriate target
What is the definition of lack of response in pharmacogenetics?
Target does not respond or drug is metabolized or excreted too rapidly
What are phenotypic approaches in identifying pharmacogenetic polymorphisms?
Can get information about physical characteristics such as enzyme activity and patterns of drug metabolism
What are the limitations of phenotypic approaches?
- Accessibility of tissue
- Difficulty in studying drug metabolites
- Challenges in studying drug receptors
What do genotypic approaches study?
Gene of pharmacological relevance for the presence of genetic polymorphisms
What are the advantages of genotypic approaches?
- Directly examining the gene of interest
- Using various sources for DNA
What are the disadvantages of genotypic approaches?
- Need to relate polymorphisms to function
- Technically complex
