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91 Cards in this Set

  • Front
  • Back
Which of the following transporters is most likely to limit bioavailability of digoxin?
a. Breast cancer resistance protein (ABCG2)
b. P‐glycoprotein (ABCB1)
c. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP‐C)
d. Organic anion transporting polypeptide 1B3 (OATP1B3; OATP‐8)
e. Organic anion transporting polypeptide 2B1 (OATP2B1; OATP‐B)
f. Multidrug resistance‐associated protein 2 (MRP2; ABCC2)
b. P‐glycoprotein (ABCB1)
Breast Cancer Resistance Protein (BCRP) is expressed at the blood‐brain barrier and efficiently transports imatinib. Inhibition of BCRP would be expected to have what effect on the concentration of imatinib achieved in brain tissue relative to plasma?
a. Increased imatinib brain concentration.
b. Decreased imatinib brain concentration.
a. Increased imatinib brain concentration.
Transport‐based drug interactions with pravastatin are most likely mediated through which of the following transporters?
a. Breast cancer resistance protein (ABCG2)
b. P‐glycoprotein (ABCB1)
c. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP‐C)
d. Organic anion transporting polypeptide 1B3 (OATP1B3; OATP‐8)
e. Organic anion transporting polypeptide 2B1 (OATP2B1; OATP‐B)
f. Multidrug resistance‐associated protein 2 (MRP2; ABCC2)
c. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP‐C)
The magnitude of CYP enzyme induction caused by rifampin may be affected by genetic variation in which of the following transporters?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MRP2 (ABCC2)
d. OATP1B1 (SLCO1B1)
e. OCTN1 (SLC22A4)
f. None of the above.
d. OATP1B1 (SLCO1B1)
Antipsychotic‐induced weight gain is associated with polymorphisms in the gene that encodes for which of the following?
a. Arachidonate 5‐lipoxygenase‐activating protein
b. Factor V
c. Leptin
d. Serotonin receptor
e. Major histocompatability complex
f. Vitamin D receptor
g. Vitamin K epoxide reductase
d. Serotonin receptor
Which of the following BEST summarizes what is known about CYP3A5 and P‐glycoprotein pharmacogenetic associations with calcineurin/ mammalian target of rapamycin inhibitors?
a. Cyclosporine dose requirements are larger in CYP3A5 expressors but the doses of tacrolimus and sirolimus are not affected by CYP3A5 expression. P‐glycoprotein genotype influences sirolimus dose requirements, affects the cyclosporine dose requirements only in CYP3A5 non‐expressors, and is not associated with tacrolimus dose requirements.

b. Cyclosporine dose requirements are smaller in CYP3A5 expressors but the doses of tacrolimus and sirolimus are not affected by CYP3A5 expression. P‐glycoprotein genotype influences tacrolimus dose requirements, affects the cyclosporine dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

c. Cyclosporine dose requirements are not affected by CYP3A5 expression but tacrolimus and sirolimus dose requirements are larger in CYP3A5 expressors. P‐glycoprotein genotype may influence cyclosporine dose requirements, affects the tacrolimus dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

d. Cyclosporine dose requirements are not affected by CYP3A5 expression but tacrolimus and sirolimus dose requirements are smaller in CYP3A5 expressors. P‐glycoprotein genotype may influence sirolimus dose requirements, affects the tacrolimus dose requirements only in CYP3A5 expressors, and is not associated with cyclosporine dose requirements.
c. Cyclosporine dose requirements are not affected by CYP3A5 expression but tacrolimus and sirolimus dose requirements are larger in CYP3A5 expressors. P‐glycoprotein genotype may influence cyclosporine dose requirements, affects the tacrolimus dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.
Statement #1: Mycophenolic acid acyl‐glucuronide plasma concentrations associate with the UGT1A9 genotype.
Statement #2: Sirolimus nephrotoxicity associates with the ABCB1 genotype.
a. both statements 1 and 2 are true
b. both statements 1 and 2 are false
c. only statement 1 is true
d. only statement 2 is true
b. both statements 1 and 2 are false
Genetic variation in which of the following targets has NOT been shown to affect the in vitro and/or in vivo pharmacodynamics of an immunosuppressant?
a. Calcineurin
b. Inosine monophosphate dehydrogenase
c. Mammalian target of rapamycin
d. all of the above
e. a and b
f. a and c
g. b and c
h. none of the above
f. a and c
Statement #1: MRP2 (ABCC2) is involved in enterohepatic circulation of mycophenolic acid.
Statement #2: In kidney‐transplant patients treated with cyclosporine, the ABCB1 genotype of the recipient is more predictive of nephrotoxicity than the ABCB1 genotype of the donor.
a. both statements 1 and 2 are true
b. both statements 1 and 2 are false
c. only statement 1 is true
d. only statement 2 is true
c. only statement 1 is true
What information would you use to inform a dosage recommendation for a patient receiving irinotecan for the treatment of colon cancer?
a. Utilize FDA recommended precise dosage reductions for all UGT1A1 variant carriers
b. 7 tandem TA repeats in the promoter of UGT1A1 are associated with increased risk of severe leucopenia
c. 6 tandem TA repeats in exon 4 of UGT1A1 are associated with increased risk of severe leucopenia
d. The prevalence of TA tandem repeat variation within UGT1A1 is greatest in Asian populations
b. 7 tandem TA repeats in the promoter of UGT1A1 are associated with increased risk of severe leucopenia
Reviewing tamoxifen pharmacogenetic information, which of the following is NOT true?
a. Patients with a high recurrence score as predicted from the Oncotype DX are likely to receive more benefit from tamoxifen than adjuvant chemotherapy
b. CYP2D6 poor metabolizers will likely receive less benefit from tamoxifen
c. Six to 10% of Caucasian populations are classified as CYP2D6 poor metabolizers
d. There is a documented gene‐dose effect regarding tamoxifen metabolite plasma concentrations and CYP2D6
a. Patients with a high recurrence score as predicted from the Oncotype DX are likely to receive more benefit from tamoxifen than adjuvant chemotherapy
You receive the genotyping analysis for EGFR mutations in a patient with non‐small cell lung cancer, what information would you use to inform a treatment decision?
a. Exon 19 deletions and the L858R mutation have the best data supporting sensitivity to gefitinib
b. Germline mutations are important predictors of gefitinib sensitivity
c. EGFR variants known as double mutants have the best data supporting sensitivity to gefitinib
d. The positive predictive value of EGFR genotyping makes it a poor resource for determining sensitivity to gefitinib
a. Exon 19 deletions and the L858R mutation have the best data supporting sensitivity to gefitinib
A physician inquires about why pharmacogenetic based dosing for TPMT is important. To appropriately address this question, you state:
a. Wild‐type TPMT results in decreased drug inactivation
b. Variant TPMT carriers are at a greater risk for severe myelosuppression
c. Up to 50% of the population is heterozygous for TPMT variations, and routinely require large dose reductions
d. Mercaptopurine (6‐MP) is inactivated by HGPRT
b. Variant TPMT carriers are at a greater risk for severe myelosuppression
Drug X is metabolized exclusively by CYP2C8. Drug X exhibits a decreased drug effect in patients who are carriers of the CYP2C8*3 allele. Potential explanations for this genotype effect include all of the following except:
a. The protein coded by CYP2C8*3 has greater specificity for drug X than wild type CYP2C8.
b. Drug X is a prodrug.
c. The CYP2C8*3 allele is in linkage disequilibrium with another variant in the pharmacodynamic target of drug X.
d. The CYP2C8*3 allele increases expression and thus metabolism of drug X.
d. The CYP2C8*3 allele increases expression and thus metabolism of drug X.
Pharmacogenomics is most applicable to the clinical treatment of which disease?
a. Type 1 diabetes
b. Type 2 diabetes
c. Monogenic diabetes
d. Diabetes insipidus
c. Monogenic diabetes
Which of the following drugs is paired with a gene that has a variant NOT shown to affect its pharmacokinetics?
a. Glimepride CYP2C9
b. Metformin SLC22A1
c. Nateglinide SLCO1B1
d. Repaglinide CYP2C8
c. Nateglinide SLCO1B1
Which of the following drugs is paired with a gene that has a variant NOT shown to affect its pharmacodynamics?
a. Glipizide KCNJ11
b. Repaglinide KCNJ11
c. Pioglitazone PPARG
d. Glimepride ABCC8
b. Repaglinide KCNJ11
Disadvantages of whole genome association studies (GWAS) compared to candidate gene studies include all of
the following except:
a. Large sample size is required
b. Biased by previous findings
c. Replication of the association is essential
d. Expensive
b. Biased by previous findings
Which of the following does NOT describe/apply to candidate gene approach in pharmacogenetic investigations?
a. is useful in the study of genetic influences on a complex trait or disease state
b. evaluates genetic influence of genes that are likely to be involved or ‘usual suspects’
c. includes scanning the genome to discover genetic variations associated with a trait or disease state
d. candidate genes include those that may affect the pharmacokinetic or pharmacodynamic response to drugs
e. all of the above describe/apply to the candidate gene approach
c. includes scanning the genome to discover genetic variations associated with a trait or disease state
Which of the following would be a candidate gene or gene product for pharmacogenetic investigation within a disease state?
a. drug targets
b. metabolism enzymes
c. drug transporters
d. gene products that mediate adverse drug reactions
e. all of the above
e. all of the above
Which enzyme has a clear phenotypic/genotypic relationship for metabolic status and number of functional
alleles?
a. CYP1A2
b. CYP2D6
c. CYP3A4
d. UGT1A4
e. UGT1A6
b. CYP2D6
What characteristics are required of a trait or disease state to allow for pharmacogenetic investigation?
1. the disease should be a Mendelian disease, or caused by a single mutation
2. high variability in drug response among individuals
3. validated measures
4. high prevalence
5. clinically available pharmacogenetic tests
a. 1, 2, and 3
b. 1, 2, 3, and 5
c. 2, 3, and 5
d. 2, 3, and 4
e. all of the above
d. 2, 3, and 4
Genetic variation of CYP2D6 has been associated with pain and opioid response. How is this explained?
a. increased metabolic activity causes increased opiate clearance and decreased analgesia
b. decreased metabolic activity causes decreased opiate clearance and increased analgesia
c. increased metabolic activity causes increased conversion to active metabolites and increased analgesia
d. decreased metabolic activity causes decreased conversion to active metabolites and increased analgesia
e. all of the above
c. increased metabolic activity causes increased conversion to active metabolites and increased analgesia
What black box warning involving pharmacogenetics was recently added to the prescribing information of carbamazepine?
a. CYP2C9 for increased incidence of suicidal ideation
b. P‐gp for increased seizure activity
c. SCN1A for increased risk of stroke
d. HLA‐B for increased dermatologic reactions
e. UGT2B7 for increased risk of neutropenia
d. HLA‐B for increased dermatologic reactions
An example of genetic variation within the efflux transporter P‐glycoprotein and phenobarbital in which serum concentrations were identical between groups, but efficacy varied between groups. Which of the following explain this?
a. increased P‐glycoprotein activity was associated with increased transport into the blood‐brain barrier and increased CSF concentrations
b. increased P‐glycoprotein activity was associated with increased transport out of the blood‐brain barrier and decreased CSF levels
c. decreased P‐glycoprotein activity was associated with increased transport into the blood‐brain barrier and increased CSF concentrations
d. decreased P‐glycoprotein activity was associated with increased transport out of the blood‐brain barrier and decreased CSF levels
e. all of the above
b. increased P‐glycoprotein activity was associated with increased transport out of the blood‐brain barrier and decreased CSF levels
Which of the following is/are FALSE regarding P‐glycoprotein (P‐gp)?
a. P‐gp transports drugs out of cells
b. P‐gp contributes to drug resistance
c. P‐gp is present at the blood‐brain barrier
d. P‐gp can affect efficacy of drugs
e. all of the above are true regarding P‐glycoprotein
e. all of the above are true regarding P‐glycoprotein
True/False
The Genetic Information Nondiscrimination Act of 2008 (GINA) prohibits discrimination in health coverage and employment on the basis of genetic information. However, the protections do not apply to genetic information collected or acquired as part of research, defined as genetic services or participation in clinical research that includes genetic services (genetic testing, counseling, or education) by an individual or family member.
False
Haga and Burke (Genet Med. 2008 Jun;10(6):391‐5) proposed a classification scheme for pharmacogenetic tests in order to identify and prioritize the policy issues that will need to be addressed to ensure appropriate delivery of pharmacogenetics testing. Which of the following is NOT one of the criteria they proposed as a basis for classification of a pharmacogenetics test?
a. Whether the test is intended to address a current specific clinical question or to provide
information for future clinical care
b. Whether the test identifies an acquired or inherited variant
c. Whether the test results are portable and retrievable
d. Whether the test reveals ancillary clinical information
c. Whether the test results are portable and retrievable
TRUE (A) or FALSE (B). The Genetic Information Nondiscrimination Act (GINA) of 2008 protects Americans against discrimination based on their genetic information when it comes to health insurance AND employment.
True
Pravastatin pharmacokinetics is affected by genetic variation in which of the following transporters?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MDR1 (ABCB1)
d. MRP2 (ABCC2)
e. MRP3 (ABCC3)
f. OATP1B1 (SLCO1B1)
g. OATP1B3 (SLCO1B3)
h. OATP2B1 (SLCO2B1)
i. OCTN1 (SLC22A4)
j. None of the above
f. OATP1B1 (SLCO1B1)
A polymorphism in the ABCB1 gene, which encodes for the transporter P‐glycoprotein, that results in reduced activity (i.e., reduced transporter function) would be predicted to have which of the following effects on digoxin pharmacokinetics?
a. Decreased bioavailability and decreased renal clearance.
b. Increased bioavailability and increased renal clearance.
c. Decreased bioavailability and increased renal clearance.
d. Increased bioavailability and decreased renal clearance.
e. Genetic variation in ABCB1 would not affect digoxin pharmacokinetics.
d. Increased bioavailability and decreased renal clearance.
Which of the following have genetic polymorphims that associate with variation in phenytoin response due to alterations in pharmacokinetics or pharmacodynamics?
a. CYP2C9
b. CYP2C19
c. P‐glycoprotein
d. SCN1A
e. all of the above
f. a and b
g. a and c
h. a and d
i. none of the above
e. all of the above
The efficacy of phenobarbital in epilepsy was shown to be worse in carriers of the wild type allele for P‐glycoprotein (3435 C>T) as compared to carriers of the variant allele. However, serum blood phenobarbital concentrations were the same. Why was the efficacy worse?
a. The wild type P‐glycoprotein has negative effects on neurotransmitters, which would not show a difference in phenobarbital concentrations
b. Although the serum blood concentrations were the same, the CSF concentrations were different due to differences in drug efflux at the blood‐brain barrier
c. The 3435 C>T SNP of P‐glycoprotein is known to be linked to SNPs of the GABA receptor, which would not affect Phenobarbital concentrations
d. All of the above
e. None of the above
b. Although the serum blood concentrations were the same, the CSF concentrations were different due to differences in drug efflux at the blood‐brain barrier
Recently, a Black Box Warning was added for serious dermatologic reactions in patients who carry HLA‐B*1502. This warning is specific for :
a. phenytoin in patients of African ancestry
b. phenytoin in patients of Asian ancestry
c. carbamazepine in patients of African ancestry
d. carbamazepine in patients of Asian ancestry
e. all of the above
f. none of the above
d. carbamazepine in patients of Asian ancestry
The cytochrome 450 (CYP) enzyme with the most evidence of association with antidepressants is?
a. CYP1A2
b. CYP2C9
c. CYP2D6
d. CYP2C19
e. CYP3A4
c. CYP2D6
The treatment of schizophrenia could potentially benefit from pharmacogenetics because:
a. The current treatment response is poor
b. The presentation of the disease is highly variable in individuals
c. Validated scales for symptoms and side effects are available
d. The drug targets for schizophrenia are clearly identified and the genetic variation is understood
e. All of the antipsychotics are metabolized by CYP2D6
f. all of the above
g. a and b
h. a, b, and c
i. a, b, c, and d
h. a, b, and c
Which of the following is an example of a tumor genome‐related mechanism of cancer treatment failure? A polymorphism in:
a. Carboxylase (CE) which prevents irinotecan from being activated to SN‐38.
b. Thiopurine S‐methyltransferase (TPMT) which prevents metabolism of thioguanine analogs.
c. P‐glycoprotein (P‐gp or MDR1) causing increased drug efflux from a solid organ tumor.
d. Thymidylate synthase (TS, site of action for 5‐FU) leading to decreased TS activity in tumor.
c. P‐glycoprotein (P‐gp or MDR1) causing increased drug efflux from a solid organ tumor.
Based on the pharmacogenetic‐driven 6‐mercaptopurine dosing scheme presented in class, which dosing scheme would MOST LIKELY be seen in a TPMT pharmacogenetic‐derived dosing scheme for Azathioprine? [Homozygous wildtype = WT, homozygous mutant = mut, heterozygous = het, standard dose = sd]
a. WT: 100% sd; het: 50%; mut: 50%
b. WT: 100% sd; het: 50%; mut: 10%
c. WT: 90% sd; het: 50%; mut: 10%
d. WT: 50% sd; het: 50%; mut: 10%
e. WT: 10% sd; het: 50%; mut: 100%
b. WT: 100% sd; het: 50%; mut: 10%
Which of the following statements is FALSE regarding thiopurine S‐methyltransferase (TPMT)?
a. TPMT is a major metabolic enzyme for mercaptopurine, thioguanine, and azathioprine.
b. TPMT genetic variants are associated with both efficacy and toxicity in response to thioguanine analogs.
c. Patients with the *3/*3 genotype (homozygous variant) require an empirical reduction in 6‐MP dose.
d. Mutant homozygotes have less TPMT activity than heterozygotes.
e. All of the above are false
f. None of the above are false
f. None of the above are false
Which of the following BEST summarizes what is known about CYP3A5 and P‐glycoprotein pharmacogenetic associations with calcineurin/ mammalian target of rapamycin inhibitors?
a. Tacrolimus and sirolimus dose requirements are larger in CYP3A5 expressors but the dose of cyclosporine is not affected. P‐glycoprotein genotype influences cyclosporine dose requirements, affects the tacrolimus dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.

b. Tacrolimus and sirolimus dose requirements are smaller in CYP3A5 expressors but the dose of cyclosporine is not affected. P‐glycoprotein genotype influences sirolimus dose requirements, affects the tacrolimus dose requirements only in CYP3A5 expressors, and is not associated with cyclosporine dose requirements.

c. Cyclosporine dose requirements are larger in CYP3A5 expressors but the doses of tacrolimus and sirolimus are not affected by CYP3A5 expression. P‐glycoprotein genotype influences sirolimus dose requirements, affects the cyclosporine dose requirements only in CYP3A5 non‐expressors, and is not associated with tacrolimus dose requirements.

d. Cyclosporine dose requirements are smaller in CYP3A5 expressors but the doses of tacrolimus and sirolimus are not affected by CYP3A5 expression. P‐glycoprotein genotype influences tacrolimus dose requirements, affects the cyclosporine dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.
a. Tacrolimus and sirolimus dose requirements are larger in CYP3A5 expressors but the dose of cyclosporine is not affected. P‐glycoprotein genotype influences cyclosporine dose requirements, affects the tacrolimus dose requirements only in CYP3A5 non‐expressors, and is not associated with sirolimus dose requirements.
he ABCB1 genotype is associated with the risk of nephrotoxicity for which of the following immunosuppressants?
a. Cyclosporine
b. Mycophenolic acid
c. Sirolimus
d. all of the above
e. a and b
f. a and c
g. b and c
h. none of the above
a. Cyclosporine
Genetic variation in which of the following targets has been shown to affect the in vitro and/or in vivo
pharmacodynamics of an immunosuppressant?
a. Calcineurin
b. Mammalian target of rapamycin
c. Inosine monophosphate dehydrogenase
d. all of the above
e. a and b
f. a and c
g. b and c
h. none of the above
c. Inosine monophosphate dehydrogenase
The landmark studies by Materson et al., published 1993‐1995, showed which of the following?
a. Response to lipid lowering therapy is variable based upon race
b. Response to anticoagulation therapy is variable based upon VCORC1 status
c. Response to antihypertensive therapy across commonly used classes of drugs is variable across
races regardless of age
d. Response to anti‐arrhythmic therapy is variable based upon electrolyte channels
c. Response to antihypertensive therapy across commonly used classes of drugs is variable across races regardless of age
The presence β1‐49 and β1‐389 codon polymorphisms were grouped to form diplotypes in the paper published by Johnson et al., mentioned in lecture 1 of the CV pharmacogenetics series. Which of the following best describes the results presented?
a. β1‐49 and β1‐389 diplotypes were equally distributed among blacks and whites enrolled in the study
b. β1‐389 codon polymorphisms were associated with variable pharmacokinetic properties of metoprolol
c. Patients with wild type copies of both alleles (SR/SR) experienced a greater blood pressure response compared to variant carriers
d. β1‐49 and β1‐389 diplotypes were not predictive of blood pressure response or pharmacokinetic properties of metoprolol
c. Patients with wild type copies of both alleles (SR/SR) experienced a greater blood pressure response compared to variant carriers
Based upon the findings from the paper presented entitled “The APOE ε4 allele determines prognosis and the effect on Prognosis of Simvastatin in Survivors of MI” it can be generalized that:
a. ε2 allele carriers have a poorer prognosis compared to other APOE allele carriers and are likely to benefit from statins post–MI
b. ε4 allele carriers have a better prognosis and are less likely to benefit from statins post–MI
c. ε4 allele carrier status was not a significant predictor for survival pre or post statin therapy
d. ε4 allele carriers have a poorer prognosis when untreated compared to other APOE allele
carriers and are likely to benefit from statins post–MI
d. ε4 allele carriers have a poorer prognosis when untreated compared to other APOE allele
carriers and are likely to benefit from statins post–MI
VKORC1 polymorphisms have been associated with which of the following?
a. S‐warfarin plasma concentrations
b. R‐warfarin plasma concentrations
c. Warfarin weekly dose requirements
d. all of the above
e. a and b
f. a and c
g. b and c
c. Warfarin weekly dose requirements
The assigned reading by Frere et al., was a large clopidogrel pharmacogenetic study that suggested which of the following results?
a. CYP3A4*1B polymorphisms associate with clopidogrel response
b. CYP2C19*2 allele carriers have higher platelet reactivity (lower platelet response) after a loading dose of clopidogrel
c. Homozygous carriers of CYP2C19*2 had higher platelet reactivity compared to heterozygous carriers (Gene dose effect)
d. all of the above
e. a and b
f. a and c
g. b and c
g. b and c
Which of the following statements regarding safety biomarkers is TRUE?
a. Safety biomarkers predict drug toxicity and susceptibility to drug-related injuries.
b. Safety biomarkers predict therapeutic response to drugs.
c. Safety biomarkers can be used to screen out non-responder patients.
d. None of the above
a. Safety biomarkers predict drug toxicity and susceptibility to drug-related injuries.
The ratio of debrisoquine to the metabolite 4-hydroxydebrisoquine (DB/4OH-DB) has
frequently been used as an index of CYP2D6 activity. The ratio is calculated from the amount
of drug and metabolite recovered in urine over a defined time period. Which of the following
statements regarding this index is TRUE?

a. The DB/4OH-DB ratio will be higher in individuals with the *1/*1 CYP2D6 genotype than in individuals with the *4/*4 CYP2D6 genotype.
b. Ultrarapid metabolizers have higher values of the DB/4OH-DB ratio than Intermediate metabolizers.
c. The DB/4OH-DB ratio is largest in CYP2D6 Poor Metabolizers.
d. All of the above
e. A and B
f. A and C
g. B and C
c. The DB/4OH-DB ratio is largest in CYP2D6 Poor Metabolizers.
Which of the following statements regarding CYP2C pharmacogenetics is TRUE?
a. The CYP2C9*3 allele is a “loss-of-function” or non-functional allele.
b. The CYP2C9*2 allele is more common in Caucasians than African-Americans.
c. Voriconazole pharmacokinetics does not differ by CYP2C19 genotype.
d. H. pylori cure rate with triple therapy (antibiotics with omeprazole) is higher in
CYP2C19 poor metabolizers.
e. Two of the above are true.
f. Three of the above are true.
g. All of the above are true.
e. Two of the above are true.
Tacrolimus dose requirements have been associated with the genotype for which of the following CYP enzymes?
a. CYP1A2
b. CYP2A6
c. CYP2C8
d. CYP2C9
e. CYP2C19
f. CYP2D6
g. CYP3A4
h. CYP3A5
h. CYP3A5
Which of the following statements regarding UGT1A1*28 is/are TRUE?

a. UGT1A1*28 is a variant allele associated with increased gene expression and increased
glucuronidation.
b. A majority of the population is homozygous for UGT1A1*28.
c. Individuals with a homozygous UGT1A1*28 genotype are at greater risk for neutropenia with irinotecan (Camptosar).
d. A and B
e. A and C
f. B and C
c. Individuals with a homozygous UGT1A1*28 genotype are at greater risk for neutropenia with irinotecan (Camptosar).
A polymorphism that results in reduced activity (i.e., reduced transporter function) was discovered in the ABCG2 gene, which encodes for the transporter Breast Cancer Resistance
Protein (BCRP). Similar to P-glycoprotein, BCRP is expressed in the intestine and blood brain barrier. Which of the following could be a potential consequence of variation in the ABCG2 gene?
a. Decreased oral absorption of mitoxantrone and methotrexate.
b. Increased oral absorption of mitoxantrone and methotrexate.
c. Decreased brain penetration of BCRP substrate drugs (e.g., imatinib).
d. Increased brain penetration of BCRP substrate drugs (e.g., imatinib).
e. A and C
f. A and D
g. B and C
h. B and D
h. B and D
Drug-drug interactions with digoxin are typically mediated through which of the following transporters?
a. Breast cancer resistance protein (ABCG2)
b. Dipeptide transporter (hPepT1)
c. P-glycoprotein (ABCB1)
d. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP-C)
e. Organic anion transporting polypeptide 1B3 (OATP1B3; OATP-8)
f. Organic anion transporting polypeptide 2B1 (OATP2B1; OATP-B)
g. Multidrug resistance-associated protein 2 (MRP2; ABCC2)
c. P-glycoprotein (ABCB1)
Abacavir hypersensitivity has been associated with genetic variation in which of the following genes?
a. ALOX5
b. CRHR1
c. HLA subtype B
d. Prothrombin
e. VKORC1
f. None of the above
c. HLA subtype B
A polymorphism in the SCN1A gene (sodium channel) was the first polymorphism in a drug
target associated with differential dosage requirements in clinical use of which of the following drug classes?
a. Analgesics
b. Antidepressants
c. Antiepileptics
d. Antipsychotics
e. All of the above
f. None of the above
c. Antiepileptics
A variant allele of the MC1R gene (Melanocortin-1 receptor), usually associated with hair and skin pigmentation, is also associated with which of the following?
a. Antipsychotic effects
b. Analgesic effects
c. Antiepileptic effects
d. Antidepressant effects
e. All of the above
f. None of the above
b. Analgesic effects
Which of the following genes may affect feeding behavior and weight gain with use of
antipsychotics?

a. 5-HT2A
b. 5-HT2C
c. ABCB1
d. DRD2
e. a&b
f. b&c
g. All of the above
h. None of the above
b. 5-HT2C
Which of the following is an example of a commercially available American Society of Clinical Oncology (ASCO) recommended pharmacogenetic test?
a. Luminex 100
b. Oncotype DX
c. Genotype DX
d. Applied Biosystems 7300 RT
e. None of the above
b. Oncotype DX
Based on the pharmacogenetic-driven 6-mercaptopurine dosing scheme presented in class,
which dosing scheme would MOST LIKELY be seen in a TPMT pharmacogenetic-derived
dosing scheme for Azathioprine? [Homozygous wildtype = WT, homozygous mutant = mut,
heterozygous = het, standard dose = sd]
a. WT: 100% sd; het: 50%; mut: 50%
b. WT: 90% sd; het: 50%; mut: 10%
c. WT: 50% sd; het: 50%; mut: 10%
d. WT: 10% sd; het: 50%; mut: 100%
e. WT: 100% sd; het: 50%; mut: 10%
e. WT: 100% sd; het: 50%; mut: 10%
Choose the MOST LIKELY mechanism(s) of why cancer treatments can fail.
a. Tumor cell over-expresses metabolizing enzyme of drug
b. Tumor cell under-expresses co-factor to drug metabolizing enzyme.
c. Tumor cell over-expresses transport enzyme which pumps drug out of cell
d. a and b
e. a and c
e. a and c
Which of the following statements regarding CYP2D6 is/are TRUE?
a. Approximately 5% of drugs are metabolized by CYP2D6.
b. CYP2D6 poor metabolizers are more common in Caucasian populations than
Asian populations.
c. CYP2D6 poor metabolizers would have lower plasma concentrations of the
antidepressant nortriptyline compared to ultrarapid metabolizers.
d. None of the above.
e. All of the above.
b. CYP2D6 poor metabolizers are more common in Caucasian populations than
Asian populations.
Which of the following statements regarding CYP3A4 and CYP3A5 is/are TRUE?
a. SNPs in CYP3A5 have more functional relevance than SNPs in CYP3A4.
b. CYP3A5 is a minor contributor to drug metabolism, even in individuals who are
homozygous carriers of CYP3A5*1.
c. SNPs in CYP3A4 (e.g., CYP3A4*1B) have been shown to affect dose-normalized tacrolimus concentrations.
d. None of the above.
e. All of the above.
a. SNPs in CYP3A5 have more functional relevance than SNPs in CYP3A4
Which of the following transporters plays an important role in the pharmacokinetics of pravastatin and rosuvastatin?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MDR1 (ABCB1)
d. MRP2 (ABCC2)
e. MRP3 (ABCC3)
f. OATP-C (SLC21A6)
g. None of the above.
f. OATP-C (SLC21A6)
A polymorphism that results in reduced activity (i.e., reduced transporter function) was
discovered in the ABCB1 gene, which encodes for the transporter P-glycoprotein. Which of the following could be a potential consequence of this genetic variation?
a. Decreased oral absorption of drugs that are P-glycoprotein substrates.
b. Decreased exposure in the brain of drugs that are P-glycoprotein substrates.
c. Increased oral absorption of drugs that are P-glycoprotein substrates.
d. Increased exposure in the brain of drugs that are P-glycoprotein substrates.
e. A and B
f. A and D
g. B and C
h. C and D
h. C and D
Antipsychotic induced weight gain has been associated with polymorphisms in which of
the following receptors?
a. β1-adrenergic receptor (β1AR)
b. β2- adrenergic receptor (β2AR)
c. Histamine H1 receptor
d. Serotonin 5-HT2C receptor
e. None of the above.
d. Serotonin 5-HT2C receptor
hich of the following is most likely to be a mechanism of cancer treatment failure?
A polymorphism that results in:
a. Decreased carboxylase (CE) activity
b. Decreased thiopurine S-methyltransferase (TPMT) activity
c. Decreased P-glycoprotein (P-gp or MDR1) activity
d. Decreased UGT1A1 activity
a. Decreased carboxylase (CE) activity
Carbamazepine is primarily metabolized by which of the following CYP enyzme(s)?
a. CYP2C9
b. CYP2C19
c. CYP3A4
d. A and B
e. A, B and C
c. CYP3A4
Which of the following statements is/are TRUE?
a. The maximum dose of phenytoin is not different in patients who carry the
CYP2C9*3 allele.
b. The maximum dose of carbamazepine is reduced in patients who carry the CYP2C9*3 allele.
c. The ABCB1 3435C>T (P-glycoprotein) genotype is not associated with dosing
requirements for phenytoin.
d. The ABCB1 3435C>T (P-glycoprotein) genotype is associated with adverse effects to carbamazepine.
e. A and C
f. B and D
g. none of the above
c. The ABCB1 3435C>T (P-glycoprotein) genotype is not associated with dosing
requirements for phenytoin.
The SCN1A polymorphism is of general importance because:
a. of its demonstrated role in pharmacoresistance to carbamazepine therapy
b. of the prominence of sodium channel blockade in treatment of epilepsy
c. of its relationship to the expression of p-glycoprotein
d. all of the above
b. of the prominence of sodium channel blockade in treatment of epilepsy
SNPs/Haplotypes in the VKORC1 gene have been associated with variable response to what drug?
a. Metoprolol
b. Hydrochlorothiazide
c. Simvastatin
d. Warfarin
d. Warfarin
he β1-389 and 49 polymorphisms have been associated with which of the choices below?
a. Variable pharmacokinetics with warfarin
b. Variable pharmacodynamic response to warfarin
c. Variable pharmacokinetics with metoprolol
d. Variable pharmacodynamic response to metoprolol
d. Variable pharmacodynamic response to metoprolol
In 1995, Materson et al. reported which of the following findings in the New England
Journal of Medicine?
a. APOE variant alleles are associated with increased risk for MI
b. Approximately 50% of patients achieve desired BP goals after initial treatment
with antihypertensive agents
c. Weekly dosage requirements for patients on warfarin therapy is associated with CYP2C9 genotypes
d. α-adducin genotype was associated with variable response to
hydrochlorothiazide
b. Approximately 50% of patients achieve desired BP goals after initial treatment
Which of the following would not be considered an ethical, legal or social concern with the use of genotype in medical practice?
a. the possibility of health and life insurance companies denying coverage to individuals with certain rare or more costly genotypes.
b. the uncertainty that arises if genetic disorders are diagnosed which are either
symptom less or where no effective interventions are yet available to improve their outcome.
c. the proper roles for the various health professionals dealing with
pharmacogenomics.
d. the social consequences of using racial or ethnic categories in research and clinical care.
e. the observation that racial characteristics correlate better with biological processes than genotype.
e. the observation that racial characteristics correlate better with biological processes than genotype.
True (A) or false (B). The ability to predict response to pharmacological treatment or to diagnose a genetic disorder from a single gene or gene mutation is only probabilistic and does not yield definitive predictions.
True
Gene duplication has been identified for which of the following CYP enzymes?
a. CYP1A2
b. CYP2C8
c. CYP2C19
d. CYP2D6
e. CYP3A5
d. CYP2D6
A polymorphism in which of the following CYP enzymes has been shown to affect dose-
normalized tacrolimus concentrations?
a. CYP2C8
b. CYP2C9
c. CYP2D6
d. CYP3A4
e. CYP3A5
e. CYP3A5
The cure rates for Helicobacter pylori infection and peptic ulcer achieved by using
standard dual therapy has been shown to be highest in individuals carrying two copies
of variant alleles for which of the following CYP enzymes?
a. CYP1A2
b. CYP2C9
c. CYP2C19
d. CYP2D6
e. CYP3A5
c. CYP2C19
A low activity genetic variant of which of the following UGT enzymes may be a risk factor for the development of prostate cancer?
a. UGT1A1
b. UGT1A6
c. UGT1A9
d. UGT2B7
e. UGT2B15
e. UGT2B15
Genetic variation in which of the following UGT enzymes has been associated with toxicity with irinotecan therapy?
a. UGT1A1
b. UGT1A6
c. UGT1A9
d. UGT2B7
e. UGT2B15
a. UGT1A1
Which of the following transporters plays an important role in the development of
resistance and also the intestinal absorption and hepatobiliary excretion of anticancer drugs such as topetecan and mitoxantrone?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MRP2 (ABCC2)
d. MRP3 (ABCC3)
e. None of the above.
a. BCRP (ABCG2)
Which one of the following transporters is associated with Dubin-Johnson syndrome, a hereditary defect in bilirubin glucuronide elimination that leads to conjugated
hyperbilirubinemia?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MRP2 (ABCC2)
d. MRP3 (ABCC3)
e. None of the above.
c. MRP2 (ABCC2)
polymorphism that results in reduced activity (i.e., reduced transporter function) was
discovered in the ABCB1 gene, which encodes for the transporter P-glycoprotein.
Which of the following could be a potential consequence of this genetic variation?
a. Decreased oral absorption of drugs that are P-glycoprotein substrates.
b. Decreased exposure in the brain of drugs that are P-glycoprotein substrates.
c. Increased oral absorption of drugs that are P-glycoprotein substrates.
d. Increased exposure in the brain of drugs that are P-glycoprotein substrates.
e. A and B
f. A and D
g. B and C
h. C and D
h. C and D
Which of the following is an example of a novel molecularly-based “targeted” therapy for cancer?
a. Imatinib (Gleevec)
b. Irinotecan (Camptosar)
c. Mercaptopurine (Purinethol)
d. Methotrexate (Trexall)
a. Imatinib (Gleevec)
Which of the following statements is TRUE regarding thiopurine S- methyltransferase (TPMT)?
a. The TPMT pathway is not a major metabolic pathway for mercaptopurine,
thioguanine, and azathioprine.
b. TPMT genetic variants are associated with both efficacy and toxicity in response to thioguanine analogs.
c. Patients with the *1/*1 genotype (homozygous wild-type) require an empirical 65% reduction in 6-MP.
d. Mutant homozygotes have more TPMT activity than heterozygotes.
b. TPMT genetic variants are associated with both efficacy and toxicity in response to thioguanine analogs.
Which of the following groups had the BEST response to treatment with metoprolol as measured by the 24-hour blood pressure response?
a. Subjects with a homozygous haplotype in the β1-389 and β1-49.
b. Subjects with a variant allele in GNβ3.
c. Subjects with the B1B1 genotype of CETP.
d. Subjects who were α-adducin variant carriers.
a. Subjects with a homozygous haplotype in the β1-389 and β1-49.
The polymorphism in GNβ3 that has been associated with increased blood pressure
response to diuretics is which of the following?
a. A SNP.
b. A deletion.
c. A repeat of a variable number of 12 bases.
d. A polymorphism identified by the presence or absence of a restriction enzyme cutting site.
b. A deletion.
What response should be measured in a study evaluating the clinical relevance of haplotypes in the VKORC1 gene?
a. Occurrence of bleeding events in subjects taking warfarin.
b. Response to diuretic therapy with HCTZ in terms of blood pressure.
c. Prevention of secondary cardiovascular events in terms of treatment with simvastatin.
d. Mean warfarin dose required to acquire target anticoagulation intensity.
d. Mean warfarin dose required to acquire target anticoagulation intensity.
Which one of the following transporters is most likely to limit bioavailability of valacyclovir?
a. Breast cancer resistance protein (ABCG2)
b. Dipeptide transporter (hPepT1)
c. P-glycoprotein (ABCB1)
d. Organic anion transporting polypeptide 1B1 (OATP1B1; OATP-C)
e. Organic anion transporting polypeptide 1B3 (OATP1B3; OATP-8)
f. Organic anion transporting polypeptide 2B1 (OATP2B1; OATP-B)
g. Multidrug resistance-associated protein 2 (MRP2; ABCC2)
b. Dipeptide transporter (hPepT1)
Which one of the following transporters is associated with Dubin‐Johnson syndrome, a hereditary
defect in bilirubin glucuronide elimination that leads to conjugated hyperbilirubinemia?
a. BCRP (ABCG2)
b. BSEP (ABCB11)
c. MDR1 (ABCB1)
d. MRP2 (ABCC2)
e. MRP3 (ABCC3)
f. OATP1B1 (SLCO1B1)
g. OATP1B3 (SLCO1B3)
h. OATP2B1 (SLCO2B1)
i. OCTN1 (SLC22A4)
j. None of the above.
d. MRP2 (ABCC2)
Abacavir is an antiretroviral drug used for the treatment of HIV. The prescribing information includes a black box
warning regarding treatment in patients who carry a particular variant allele. Which of the following best
describes the genetic association found with abacavir?
a. Polymorphism(s) in a UGT enzyme with abacavir metabolism.
b. Polymorphism(s) in alcohol dehydrogenase and abacavir metabolism.
c. Polymorphism(s) in Apolipoprotein E4 and abacavir adherence.
d. Polymorphism(s) in the major histocompatibility complex and abacavir hypersensitivity.
e. None of the above.
d. Polymorphism(s) in the major histocompatibility complex and abacavir hypersensitivity.