pharmacogenomics Flashcards
Which of the following is a primary goal of pharmacogenomics?
A) To develop drugs that eliminate all side effects.
B) To tailor drug treatments based on genetic and non-genetic factors.
C) To ensure that all patients receive the same standard drug dose.
D) To replace traditional medicine with gene therapy.
Pharmacogenomics focuses on tailoring drug treatments to individual patients by considering genetic and non-genetic factors, as discussed under precision health.
Which genetic variation is most likely to result in an increase in enzyme activity?
A) A missense coding variation.
B) A regulatory variation that increases gene expression.
C) A splice-site variation leading to exon skipping.
D) A frameshift mutation in the coding region.
Regulatory variations can increase gene expression, leading to higher enzyme activity, whereas the other variations are more likely to disrupt normal function.
A patient is an ultrarapid metabolizer of codeine due to CYP2D6 genetic variants. What is the most likely consequence of prescribing standard doses of codeine to this patient?
A) Reduced effectiveness due to incomplete metabolism.
B) Toxic effects from rapid conversion to morphine.
C) No therapeutic effect because codeine remains inactive.
D) Complete metabolism to inactive byproducts.
Ultrarapid metabolizers convert codeine to morphine quickly, increasing the risk of toxicity, as mentioned in the CYP2D6 example.
A patient with TPMT loss-of-function alleles is prescribed mercaptopurine. What adjustment should the physician make?
A) Increase the dose to compensate for slower activation.
B) Reduce the dose to avoid myelosuppression.
C) Switch to a drug that does not require TPMT for metabolism.
D) Administer the drug more frequently at the same dose.
Patients with TPMT loss-of-function alleles metabolize mercaptopurine poorly, leading to toxicity. Dose reductions can minimize adverse effects like myelosuppression.
/
What is an expression quantitative trait locus (eQTL)?
A) A DNA variant that alters the sequence of a protein.
B) A genetic variation that affects drug metabolism rates.
C) A genetic variation that influences gene expression levels.
D) A mutation in splicing regions that disrupts RNA processing.
eQTLs are genetic variants that affect the level of gene expression, as explained under regulatory variation.
Which of the following describes the main mechanism of action for mercaptopurine?
A) It stimulates DNA replication.
B) It inhibits DNA synthesis as a purine antagonist.
C) It increases RNA transcription rates.
D) It enhances enzyme activity in metabolic pathways.
Mercaptopurine inhibits DNA synthesis by acting as a purine antagonist, a key detail mentioned in the lecture.
Why is the CYP2D6 gene considered critical in pharmacogenomics, and how do its variants impact drug therapy?
A) CYP2D6 is responsible for detoxifying all drugs in the body, and its variants lead to complete drug inactivation.
B) CYP2D6 metabolizes a wide range of drugs, and its variants can result in altered drug metabolism rates, affecting therapeutic outcomes.
C) CYP2D6 activates only opioid medications, and its variants cause uniform increases in drug metabolism.
D) CYP2D6 produces enzymes that break down proteins, and its variants have no clinical impact on drug therapy.
CYP2D6 is a key enzyme involved in the metabolism of many drugs, including opioids like codeine. Variants in this gene can lead to diverse metabolic phenotypes, such as ultrarapid, normal, intermediate, or poor metabolizers, significantly influencing the efficacy and safety of drug therapy.
b
How can regulatory genetic variations in a gene affect drug response?
A) By altering the sequence of the protein directly, changing its function.
B) By modifying the amount of the gene’s expression, leading to changes in enzyme activity.
C) By introducing premature stop codons that disrupt the protein structure.
D) By creating a splicing defect that prevents the gene from producing functional RNA.
Regulatory variations affect gene expression levels, which can alter the amount of protein (e.g., enzymes) produced. This influences drug metabolism without directly changing the protein’s sequence.
b
How might a splice-site genetic variation lead to altered drug metabolism?
A) By increasing the rate at which a gene is transcribed into RNA.
B) By producing a protein with altered amino acids but intact function.
C) By causing improper RNA splicing, leading to a non-functional or truncated protein.
D) By increasing the stability of the RNA transcript, leading to excessive protein production.
Splice-site variations can disrupt normal splicing, potentially excluding important exons or including introns in the final RNA. This results in defective proteins that may impair drug metabolism.
What is the primary consequence of a missense coding variation on a protein’s function?
A) It changes a single amino acid in the protein, potentially altering its activity.
B) It disrupts RNA splicing, leading to incomplete protein production.
C) It prevents the gene from being transcribed into RNA, reducing protein levels.
D) It removes entire exons from the gene, resulting in a truncated protein.
It changes a single amino acid in the protein, potentially altering its activity.
