Personalized Medicine Practice Exam 1 (2014)

Which of the following statements is FALSE?

A. Most drug transporters belong to the SLC family.

B. SLC transporters do not contain ATP binding sites.

C. SLC transporters are facilitative or secondary active transporters.

D. SLC transporters can transport both xenobiotics and endogenous compounds.

E. P-gp and BCRP are among the most characterized SLC transporters.

E. P-gp and BCRP are among the most characterized SLC transporters.

The function of the efflux transporter BCRP is affected by the ABCG2 polymorphism C421A. The A allele is associated with deceased expression of BCRP. How would you expect the intestinal absorption of the BCRP substrate rosuvastatin to be affected in patients carrying the A allele?

A. Decreased absorption due to decreased BCRP function

B. Deceased absorption due to increased BCRP function

C. Increased absorption due to decreased BCRP function

D. Increased absorption due to increased BCRP function

C. Increased absorption due to decreased BCRP function

The OATP2B1 transporter is expressed on the apical membrane of enterocytes in the intestine and efficiently transports fexofenadine. A genetic variant that causes decreased activity of OATP2B1 would be expected to have what effect on the bioavailability of fexofenadine?

A. Increased fexofenadine bioavailability.

B. Decreased fexofenadine bioavailability.

B. Decreased fexofenadine bioavailability.

Which of the following statement is TRUE?

A. DNA isolation from mouthwash is preferred to blood because it has a higher yield

B. Red blood cells (RBCs) are a good source for DNA isolation

C. Isolation of DNA from blood results in a higher yield than from mouthwash

D. Platelets are a good source for DNA isolation

C. Isolation of DNA from blood results in a higher yield than from mouthwash

Which of the following cells can NOT be used for DNA \ isolation?

A. lymphocytes

B. neutrophils

C. red blood cells

D. skeletal muscle cells

E. smooth muscle cells

C. red blood cells

Which of the following alleles is an example of a variable number of tandem repeats (VNTR)

polymorphism?

A. CYP2D6*4

B. CYP3A5*3

C. UGT1A1*28

D. UGT1A6*2

C. UGT1A1*28

Which of the following would you expect in N-acetyltransferase-2 (NAT2) rapid (or fast) acetylators

compared to slow acetylators?

A. Lower concentrations of isoniazid with a fixed dose.

B. A higher incidence of hydralazine-induced lupus erythematosus.

C. Faster appearance of antinuclear antibodies with procainamide.

A. Lower concentrations of isoniazid with a fixed dose.

A functionally relevant variant allele in which of the following genes has been associated with altered valproic acid pharmacokinetics?

A. UGT1A1

B. UGT1A3

C. UGT1A6

D. UGT1A9

C. UGT1A6

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 CYP2D61/1 genotype than in

individuals with the CYP2D64/4 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.

C. The DB/4OH-DB ratio is largest in CYP2D6 Poor Metabolizers.

Which of the following statements regarding CYP2A6 is TRUE?

A. There are more poor metabolizers found in Asian populations compared with Caucasian populations.

B. An individual with the genotype CYP2A61/1x2 would have slower than average nicotine clearance.

C. Homozygous carriers of the CYP2A6*4 allele have faster than average nicotine clearance.

A. There are more poor metabolizers found in Asian populations compared with Caucasian populations.

Gene duplication has been identified with which of the following CYP enzymes?

A. CYP1A2

B. CYP2C19

C. CYP2D6

D. CYP3A5

C. CYP2D6

Genetic variation producing a loss-of-function allele in the gene that encodes for which of the following enzymes is associated with decreased nicotine metabolism and decreased rate of smoking?

A. CYP1A2

B. CYP2A6

C. CYP2C19

D. CYP2D6

E. CYP3A5

B. CYP2A6

The Food and Drug Administration issued a safety alert for codeine use in children after tonsillectomy in August 2012. The risk described would be associated most with which of the following CYP2D6 genotypes?

A. CYP2D61/1

B. CYP2D61/1x3

C. CYP2D61/4

D. CYP2D64/4

B. CYP2D61/1x3

Which of the following statements regarding CYP2C19 is TRUE?

A. CYP2C19 genetic poor metabolizers are more common in Whites than Asians.

B. CYP2C19 extensive metabolizers would have lower plasma concentrations of omeprazole compared to intermediate metabolizers.

C. About 20% of drugs are metabolized by CYP2C19.

D. CYP2C19 poor metabolizers would require a higher dose of omeprazole compared to extensive metabolizers to maintain similar blood concentrations.

B. CYP2C19 extensive metabolizers would have lower plasma concentrations of omeprazole compared to intermediate metabolizers.

The clearance of tacrolimus after oral administration mostly reflects CYP3A-mediated metabolism. Which of the following statements regarding tacrolimus is FALSE?

A. On average, the weight-normalized tacrolimus dose required to maintain the same target blood concentration would be higher in Asians compared to Blacks.

B. Patients with the highest values of dose-adjusted tacrolimus blood concentrations are most likely to have the CYP3A53/3 genotype.

A. On average, the weight-normalized tacrolimus dose required to maintain the same target blood concentration would be higher in Asians compared to Blacks.

VeriStrat® test results provide important information that can help make more informed treatment decisions by identifying patient groups who may receive differential treatment benefit between single agent therapy options. This test is an example of which of the following?

A. Epigenomics

B. Transcriptomics

C. Proteomics

D. Metabolomics

C. Proteomics

Pharmacogenetics-guided therapeutic drug monitoring (TDM) may be MOST useful for which of the following drugs?

A. Ciprofloxacin

B. Gentamicin

C. Theophylline

D. Valproic acid

D. Valproic acid

Which of the following statements about genomic biomarker information included in a drug label is

FALSE?

A. The biomarker explains variability in drug exposure and/or clinical response.

B. The biomarker may be useful to identify patients at risk for adverse events.

C. The biomarker provides genotype-specific dosing.

D. The biomarker information included is limited to somatic mutations.

D. The biomarker information included is limited to somatic mutations.

Which of the following statements regarding sofosbuvir is TRUE?

A. Sofosbuvir is indicated in HCV infection commonly seen in the U.S., including genotype 1, 2, and 3 infections.

B. Alternative therapy should be considered in the presence of Q80K polymorphism.

C. Sofosbuvir is dosed twice daily.

D. Sofosbuvir does not have an active metabolite.

A. Sofosbuvir is indicated in HCV infection commonly seen in the U.S., including genotype 1, 2, and 3 infections.

Patient, MS, has HCV genotype 1a infection with Q80K polymorphism. She has not been treated for HCV infection before. Comorbid medical conditions include vitamin D deficiency, osteoporosis, and uncontrolled major depression. Which treatment option below is the recommended regimen by the AASLD/IDSA/IAS-USA guideline for this patient?

A. Sofosbuvir 400 mg/day + weight-based ribavirin + weekly PEG for 12 weeks

B. Sofosbuvir 400 mg/day + weight-based ribavirin + simeprevir 150 mg/day for 12 weeks

C. Simeprevir 150 mg/day + weight-based ribavirin + weekly PEG for 12 weeks

D. Sofosbuvir 400 mg/day + weight-based ribavirin for 12 weeks

Question thrown out.

Patient, YO, has HCV genotype 3 infection. She has not been treated for HCV infection before. Comorbid medical condition includes hypothyroidism. She is allergic to sulfa drugs. Which treatment option below is the recommended regimen by the AASLD/IDSA/IAS-USA guideline for this patient?

A. Sofosbuvir 400 mg/day + weight-based ribavirin for 12 weeks

B. Sofosbuvir 400 mg/day + weight-based ribavirin for 24 weeks

C. Simeprevir 150 mg/day + weight-based ribavirin + weekly PEG for 12 weeks

D. Sofosbuvir 400 mg/day + simeprevir 150 mg/day for 12 weeks

B. Sofosbuvir 400 mg/day + weight-based ribavirin for 24 weeks

Which statement below is TRUE regarding the IFNL3 rs12979860 polymorphism?

A. IFNL3 polymorphisms was found in NS3/4A region of HCV.

B. IFNL3 polymorphism affects the way that IFN binds to the receptor (i.e. receptor structure is modified), leading to unfavorable response in patients who carry the variant T alleles when they are treated with PEG+RBV combination.

C. Patients with rs12979860 CC genotype were more likely to achieve SVR after PEG+RBV therapy, and this trend was also seen with simeprevir+PEG+RBV therapy.

C. Patients with rs12979860 CC genotype were more likely to achieve SVR after PEG+RBV therapy, and this trend was also seen with simeprevir+PEG+RBV therapy.

Which statement below is TRUE regarding IFNL3 rs12979860 polymorphism and sofosbuvir therapy?

A. Among treatment-naïve patients infected with HCV-1 and treated with SOF+PEG+RBV triple therapy, patients with rs12979860 T minor allele had a lower SVR rate than patients with the CC genotype.

B. Patients with the CC genotype had significantly better response to SOF+RBV combination therapy.

C. IFNL3 rs12979860 genotype was predictive of response to SOF-based regimen in HCV-2/3 infection.

A. Among treatment-naïve patients infected with HCV-1 and treated with SOF+PEG+RBV triple therapy, patients with rs12979860 T minor allele had a lower SVR rate than patients with the CC genotype.

Which statement below is TRUE regarding polymorphisms in the HCV viral genome?

A. Cross-resistance has been reported among polymerase inhibitors.

B. Cross-resistance has not been reported among protease inhibitors.

C. The AASLD/IDSA/IAS-USA guideline recommends Q80K polymorphism testing before initiation of treatment with SMV+PEG+RBV regimen.

C. The AASLD/IDSA/IAS-USA guideline recommends Q80K polymorphism testing before initiation of treatment with SMV+PEG+RBV regimen.

Repeated Scenario: Over the past few years in practice, Dr. Patrick has noticed that his hypertension patients on Drug Q have been developing new onset diabetes more often than his hypertension patients on other drugs. Yet, there are still many of Dr. Patrick's patients who are on Drug Q and do not develop diabetes. Dr. Patrick would like to set up a pharmacogenomic study to see if there are any genetic variants (SNPs) that are contributing to his observation.

Dr. Patrick wants to design a study to investigate this question, but he does not know what has been

done before. What is first thing he should do?

A. Consult NCBI SNP to conduct a review of the SNPs in his candidate gene.

B. Consult PubMed to conduct a review of the primary literature.

C. Consult PharmGKB to conduct a review of the Drug Q pathway.

D. Consult OMIM to conduct a review of the disease.

B. Consult PubMed to conduct a review of the primary literature.

Repeated scenario: Over the past few years in practice, Dr. Patrick has noticed that his hypertension patients on Drug Q have been developing new onset diabetes more often than his hypertension patients on other drugs. Yet, there are still many of Dr. Patrick's patients who are on Drug Q and do not develop diabetes. Dr. Patrick would like to set up a pharmacogenomic study to see if there are any genetic variants (SNPs) that are contributing to his observation.

Dr. Patrick has completed his pharmacogenomic study and found that SNP 234 in Gene 2015 is associated with the development of new onset diabetes in patients treated with Drug Q. He wants to see if this variation (SNP) has clinical significance with other phenotypes, what database should he use?

A. NCBI ClinVar

B. NCBI SNP

C. NHGRI GWA Catalog

D. HuGE Navigator

Question thrown out

Repeated scenario: Over the past few years in practice, Dr. Patrick has noticed that his hypertension patients on Drug Q have been developing new onset diabetes more often than his hypertension patients on other drugs. Yet, there are still many of Dr. Patrick's patients who are on Drug Q and do not develop diabetes. Dr. Patrick would like to set up a pharmacogenomic study to see if there are any genetic variants (SNPs) that are contributing to his observation.

Dr. Patrick has discovered that SNP 811 in Gene 2012, has been previously associated with the development of new onset diabetes in hypertension patients taking Drug Q. Dr. Patrick wants to see what the allele frequencies are for SNP 811, what is the BEST database to use?

A. NCBI SNP

B. PharmGKB

C. UCSC Genome Browser

D. HapMap

D. HapMap

Genetic variation in DPYD, the gene that encodes dihydropyrimidine dehydrogenase (DPD), affects treatment response to fluoropyrimidines. How does the DPYD*2A variant affect the risk of toxicity and dosing recommendations with fluorouracil?

A. No increased risk in heterozygous carriers; no change in dosing regimen is recommended.

B. Slightly increased risk in heterozygous carriers; no change in dosing regimen is recommended.

C. Increased risk in homozygous carriers; the starting dose should be reduced by 50%.

D. Increased risk in homozygous carriers; alternative drug therapy is recommended.

D. Increased risk in homozygous carriers; alternative drug therapy is recommended.

Use the figure from W.E. Evans and H.L. McLeod. N Engl J Med. 2003. 348;6: 539. If a patient had a drug metabolism genotype of V/V and a drug receptor genotype of V/V, what drug response would you expect to see in this patient at a normal dose? (Figure missing. Check out the practice test.)

A. About 45% Efficacy and Moderate Toxicity (15%).

B. About 80% Efficacy and High Toxicity (80%).

C. About 10% Efficacy and Low Toxicity (5%).

D. About 10% Efficacy and High Toxicity (80%).

D. About 10% Efficacy and High Toxicity (80%).

Warfarin is an example of a drug with Pharmacogenomics-Guided Therapy as:

A. A contraindication.

B. An indication.

C. A dosing recommendation.

D. Explicit/implicit evidence that no dose adjustment is required by genotype

C. A dosing recommendation.

All of the following are challenges of Pharmacogenomic Testing, EXCEPT:

A. Pharmacogenomic tests may not always be feasible due to a slower turnaround time.

B. Pharmacogenomic tests may not always be accessible due to the providers' knowledge of the test(s).

C. Pharmacogenomic tests may not always have a high level of evidence due to many well done trials with large sample sizes.

D. Pharmacogenomic tests may not always be cost effective due to the high cost of the genetic test and/or genetic counseling.

C. Pharmacogenomic tests may not always have a high level of evidence due to many well done trials with large sample sizes.

The "Genomics and Drug Response" manuscript by L. Wang, H.L. McLeod, and R.M. Weinshilboum states that clinically relevant pharmacogenomic variants that influence a patient's response to antineoplastic therapy can be found in what genome(s)?

A. Both the tumor genome and the patient's germline genome

B. Only the tumor genome

C. Only the patient's germline genome

D. There are no clinically relevant pharmacogenomic variants that influence a patient's response to

antineoplastic therapy in any genome

A. Both the tumor genome and the patient's germline genome

Dr. Allen is studying the pharmacogenomics of ACE-inhibitor induced cough. Dr. Allen has found that a set of closely linked SNPs in the ACE gene, which tend to be inherited together, predict ACE-inhibitor induced cough in his patients. What type of analysis did Dr. Allen conduct to determine this?

A. Mutation Analysis

B. Haplotype Analysis

C. Linkage Disequilibrium Analysis

D. Population Stratification Analysis

B. Haplotype Analysis

C. Linkage Disequilibrium Analysis

Linkage Disequilibrium, LD, is measured by both D' and r2. Which one of the following statements is TRUE when comparing D' and r2?

A. If you want to use 1 SNP to predict the genotypes at another SNP, you should use r2.

B. If you want to determine the haplotype block structure of a gene, you should use r2.

C. If you want to find SNPs that your associated SNP could be 'tagging', you should ONLY use D'.

D. If you want to use 1 SNP as a proxy for another SNP, you should use D'.

A. If you want to use 1 SNP to predict the genotypes at another SNP, you should use r2.

SNP 226 is located in the coding region of Gene PAR. SNP 226 is a non-sense SNP. What are the MOST likely changes that SNP 226 causes?

A. SNP 226 affects the splicing of the gene, and leads to a change in the mRNA.

B. SNP 226 causes a premature stop codon, and leads to a change in the protein.

C. SNP 226 affects transcription factor binding, and leads to a change in the gene expression.

D. SNP 226 causes an amino acid change, and leads to a change in the protein.

B. SNP 226 causes a premature stop codon, and leads to a change in the protein.

SNP W has two alleles C and A. If SNP W has allele frequencies of C=0.70 and A=0.30 in the

population, and SNP W is in Hardy-Weinberg equilibrium; what are the expected genotype

frequencies in this population?

A. CC=0.70, CA=0.42, AA=0.30

B. CC=0.49, CA=0.21, AA=0.09

C. CC=0.70, CA=0.21, AA=0.09

D. CC=0.49, CA=0.42, AA=0.09

D. CC=0.49, CA=0.42, AA=0.09

Which of the following statements are FALSE about what we learned from the Human Genome Project?

A. Less than 2% of the genome codes for protein.

B. Almost all (99.9%) of nucleotide bases are exactly the same in all people.

C. The gene functions are known for all of the discovered genes.

D. All of the above.

C. The gene functions are known for all of the discovered genes.

Which of the following statements is FALSE:

A. Regions of condensed or tightly wrapped chromatin correspond to high levels of transcriptional activity.

B. Cytosine methylation in 5'CpG sequences in promoter regions of DNA regulates gene expression through transcriptional repression.

C. Acetylation of histone tails weakens their interaction with DNA and leads to a more open or relaxed chromatin conformation.

D. Vorinostat (SAHA) is an example of a Histone deacetyltransferase (HDAC) inhibitor.

A. Regions of condensed or tightly wrapped chromatin correspond to high levels of transcriptional activity

Which of the following is TRUE about RNA sequencing (RNA-seq):

A. RNA-seq allows us to identify novel transcripts.

B. RNA-seq does not require transcript specific probes.

C. Compared to microarrays, RNA-Seq offers a broader dynamic range of gene expression measurement.

D. All of the above are correct.

D. All of the above are correct.

Which of the following statements is FALSE:

A. Most gene expression is regulated on the level of transcription initiation (RNA polymerase II binding to the promoter region).

B. Out of ~22,000 genes in our genome, more than 95% are expressed at any given time in a tissue.

C. Alternate Splicing can generate tissue-specific transcripts.

D. The highest expressed genes are often tissue specific and related to tissue function.

B. Out of ~22,000 genes in our genome, more than 95% are expressed at any given time in a tissue.