Genetic variation and its role in pharmacology MCQs With Answer

Genetic variation and its role in pharmacology MCQs With Answer

This concise quiz collection is tailored for M.Pharm students studying Cellular and Molecular Pharmacology. It focuses on how genetic variation—single nucleotide polymorphisms, indels, copy number variants, HLA alleles, mitochondrial changes and regulatory polymorphisms—modulates drug pharmacokinetics, pharmacodynamics, efficacy and adverse reactions. Questions span clinical examples (CYP, TPMT, VKORC1, SLCO1B1, NUDT15, HLA), population-genetics principles (Hardy–Weinberg, linkage disequilibrium, haplotypes), experimental genotyping methods and implementation issues (CPIC, testing). Each MCQ is designed to deepen conceptual understanding and prepare students for applied pharmacogenomics in therapeutics and research.

Q1. What best defines a single nucleotide polymorphism (SNP) in the context of pharmacogenomics?

• A single nucleotide substitution at a specific genomic position that is common in a population
• An insertion or deletion of multiple nucleotides within a gene
• A chromosomal translocation affecting gene copy number
• A repetitive DNA expansion causing protein aggregation

Correct Answer: A single nucleotide substitution at a specific genomic position that is common in a population

Q2. Which type of genetic variation is primarily responsible for gene dosage changes that can alter drug-metabolizing enzyme activity?

• Copy number variation (CNV)
• Synonymous SNP
• Splice-site single nucleotide variant
• Short tandem repeat (STR) in noncoding DNA

Correct Answer: Copy number variation (CNV)

Q3. How does a CYP2C19 loss-of-function allele typically affect clopidogrel response?

• Reduced bioactivation of clopidogrel resulting in decreased antiplatelet effect
• Increased clopidogrel clearance and enhanced bleeding risk
• Increased formation of active metabolite leading to greater platelet inhibition
• No change in clopidogrel pharmacology because CYP2C19 is not involved

Correct Answer: Reduced bioactivation of clopidogrel resulting in decreased antiplatelet effect

Q4. Which pairing correctly assigns pharmacokinetic versus pharmacodynamic genetic influences on warfarin therapy?

• VKORC1 — pharmacodynamic; CYP2C9 — pharmacokinetic
• VKORC1 — pharmacokinetic; CYP2C9 — pharmacodynamic
• Both VKORC1 and CYP2C9 are strictly pharmacokinetic modifiers
• Both VKORC1 and CYP2C9 are pharmacodynamic targets

Correct Answer: VKORC1 — pharmacodynamic; CYP2C9 — pharmacokinetic

Q5. A TPMT-deficient patient is given standard doses of azathioprine. What is the most likely clinical consequence?

• Excessive thioguanine nucleotide accumulation leading to severe myelosuppression
• Subtherapeutic immunosuppression due to rapid drug inactivation
• Primary resistance with increased risk of infection but no hematologic toxicity
• Enhanced hepatic clearance and need for increased dosing

Correct Answer: Excessive thioguanine nucleotide accumulation leading to severe myelosuppression

Q6. Which HLA allele is strongly associated with hypersensitivity to abacavir?

• HLA-B*57:01
• HLA-A*02:01
• HLA-DRB1*15:01
• HLA-C*07:02

Correct Answer: HLA-B*57:01

Q7. The SLCO1B1 521T>C (Val174Ala) variant predisposes patients to which statin-related problem and by what mechanism?

• Increased risk of statin-induced myopathy due to reduced hepatic uptake and higher plasma statin levels
• Reduced LDL-lowering efficacy due to increased hepatic clearance of statin
• Enhanced statin-induced liver injury due to toxic metabolite formation
• Increased statin absorption from the gut leading to excessive exposure

Correct Answer: Increased risk of statin-induced myopathy due to reduced hepatic uptake and higher plasma statin levels

Q8. Which of the following is NOT an assumption of the Hardy–Weinberg equilibrium model used in population genetics?

• High mutation rate
• No natural selection
• Random mating
• No migration (gene flow)

Correct Answer: High mutation rate

Q9. What does linkage disequilibrium (LD) describe in genetic studies relevant to pharmacogenomics?

• Non-random association of alleles at two or more loci in a population
• The physical distance in base pairs between adjacent genes on a chromosome
• The rate at which a particular allele mutates to another allele over generations
• The complete independence of alleles at different loci

Correct Answer: Non-random association of alleles at two or more loci in a population

Q10. For targeted genotyping of a well-characterized SNP in a clinical lab, which technique is most commonly used because of simplicity, speed, and cost-effectiveness?

• Allele-specific PCR (e.g., TaqMan) for targeted SNP genotyping
• Whole-genome sequencing
• Chromosomal karyotyping
• Southern blotting

Correct Answer: Allele-specific PCR (e.g., TaqMan) for targeted SNP genotyping

Q11. NUDT15 loss-of-function variants are clinically important because they:

• Increase thiopurine sensitivity causing severe leukopenia, particularly in Asian populations
• Enhance mercaptopurine clearance leading to treatment failure
• Cause resistance to platinum chemotherapy
• Increase metabolism of warfarin leading to subtherapeutic INR

Correct Answer: Increase thiopurine sensitivity causing severe leukopenia, particularly in Asian populations

Q12. What are expression quantitative trait loci (eQTLs) in the context of pharmacogenomics?

• Genetic variants that influence the expression level of genes, affecting drug response
• Regions of the genome with repetitive sequences that affect protein folding
• Variants that exclusively alter amino-acid sequence without changing expression
• Transposable elements that silence drug-metabolizing enzymes

Correct Answer: Genetic variants that influence the expression level of genes, affecting drug response

Q13. Which type of mutation directly introduces a premature stop codon and typically results in truncated, nonfunctional protein?

• Nonsense mutation
• Missense mutation
• Synonymous (silent) mutation
• Frameshift by in-frame insertion

Correct Answer: Nonsense mutation

Q14. Which organization provides peer-reviewed clinical guidelines that translate genotype information into drug-dosing recommendations for clinicians?

• Clinical Pharmacogenetics Implementation Consortium (CPIC)
• World Health Organization (WHO)
• European Medicines Agency (EMA)
• Centers for Disease Control and Prevention (CDC)

Correct Answer: Clinical Pharmacogenetics Implementation Consortium (CPIC)

Q15. How is mitochondrial genetic variation inherited and why is it relevant for some drug toxicities?

• Maternally inherited; mitochondrial variants can alter oxidative phosphorylation and increase susceptibility to drug-induced mitochondrial toxicity
• Paternally inherited; they modify drug transport across the blood–brain barrier
• Mendelian autosomal dominant; they regulate nuclear drug-metabolizing enzymes
• Randomly inherited from either parent and do not affect drug response

Correct Answer: Maternally inherited; mitochondrial variants can alter oxidative phosphorylation and increase susceptibility to drug-induced mitochondrial toxicity

Q16. What is penetrance in genetics and how does it affect pharmacogenetic predictions?

• The proportion of individuals with a particular genotype who actually express the associated phenotype, influencing clinical predictive value
• The degree to which a gene is copied in the genome, determining enzyme dosage
• The speed at which a drug is metabolized by a given genotype
• The frequency of recombination between two loci on a chromosome

Correct Answer: The proportion of individuals with a particular genotype who actually express the associated phenotype, influencing clinical predictive value

Q17. What is the principal objective of a genome-wide association study (GWAS) in pharmacogenomics?

• To identify common genetic variants across the genome that are statistically associated with drug response or adverse effects
• To definitively prove causal molecular mechanisms for a drug effect in single patients
• To sequence the entire genome of every patient for clinical use
• To evaluate protein–drug binding kinetics in vitro

Correct Answer: To identify common genetic variants across the genome that are statistically associated with drug response or adverse effects

Q18. Which statement best describes a haplotype block in human genetics?

• A region of the genome with limited historical recombination where a set of common SNPs are inherited together
• A short DNA fragment used for allele-specific PCR assays
• A single SNP that fully determines a clinical phenotype
• A cluster of genes that encode the same drug-metabolizing enzyme

Correct Answer: A region of the genome with limited historical recombination where a set of common SNPs are inherited together

Q19. How can a regulatory SNP within a promoter or enhancer region alter drug response?

• By changing transcription factor binding and thus up- or down-regulating expression of genes involved in drug metabolism or targets
• By directly altering the primary amino-acid sequence of the encoded protein
• By inserting stop codons that truncate the protein product
• By changing the mitochondrial DNA replication rate

Correct Answer: By changing transcription factor binding and thus up- or down-regulating expression of genes involved in drug metabolism or targets

Q20. A patient carries multiple functional copies (gene duplication) of CYP2D6. How is this expected to affect drugs that are CYP2D6 substrates such as codeine?

• Ultrarapid metabolism leading to increased conversion of codeine to morphine and potential opioid toxicity
• Decreased metabolism producing subtherapeutic morphine levels and pain control failure
• No change because CYP2D6 duplication is always compensated by other enzymes
• Selective inhibition of CYP2D6 causing drug accumulation unrelated to copy number

Correct Answer: Ultrarapid metabolism leading to increased conversion of codeine to morphine and potential opioid toxicity

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