Pharmacogenomics Flashcards by Josh Klonoski

Which of the following is associated with efavirenz (NNRTI) toxicity?
A.CYP2B6
B.CYP2C9
C.CYP2D6
D.CYP3A
E.HLA-B*57:01
F.None of the above

A. CYP2B6

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Which CYP2B6 genotype is associated with efavirenz toxicity?
A.CYP2B64/4
B.CYP2B64/5
C.CYP2B66/6
D.CYP2B66/22
E.CYP2B622/22
F.All of the above
G.None of the above

C.CYP2B66/6

(G516T and A785G),
also CYP2B6*7 (G516T, A785G and C1459T)

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Which population has the highest prevalence of CYP2B6 poor metabolizers?
A. AA
B. Asian
C. Caucasian
D. Hispanic
E. None of the above

A. AA

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Which allele is associated with abacavir (NTRI) toxicity?
A.HLA-A31:01
B.HLA-B15:02
C.HLA-B57:01
D.HLA-B58:01
E.None of the above

C.HLA-B*57:01

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Abacavir treatment in patient with HLA-B*57:01. Which step should be taken for treatment
A. Continued monitoring
B. Decrease abacavir dosage
C. Increase dosage.
D. Use an alternative drug
E. None of the above

D. Use an alternative drug

lethal hypersensitivity reaction in 61% of people with this allele

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On which of the following viruses does maraviroc (chemokine receptor antagonist) exert its therapeutic activity?
A.CCR4-tropic HIV-1
B.CCR5-tropic HIV-1
C.CXCR4-tropic HIV-1
D.CXCR5-tropic HIV-1
E.None of the above

B.CCR5-tropic HIV-1

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Which of the following mutations are associated with resistance to HIV-1 infection?
A.CCR4-tropic HIV-1 with CCR4-Δ32
B.CCR5-tropic HIV-1 with CCR5-Δ32
C.CXCR4-tropic HIV-1 with CXCR4-Δ32
D.CXCR5-tropic HIV-1 with CXCR5-Δ32
E.None of the above

B.CCR5-tropic HIV-1 with CCR5-Δ32

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Which population has the highest frequency of THE CCR5-delta32 allele?
A. AA
B. Asian
C. Caucasian
D. Native American
E. None of the above

C. Caucasian

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Which gene affects warfarin dosing?
A.CYP2C9
B.CYP3A
C.CYP4F2
D.VKORC1
E.All of the above
F.None of the above

E.All of the above

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Which of the following VKORC1 genotypes would likely require a low starting dose of coumadin?
A.c.-1639G/G
B.c.-1639A/G
C.c.-1639A/A
D.Not sure
E. None of the above

C. c.-1639A/A

Less VKORC1 by way of promoter mutation

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Which one of the following CYP2C9 genotypes would most likely trigger excessive anticoagulation (INR&raquo_space;3)?
A.CYP2C91/CYP2C91
B.CYP2C92/CYP2C92
C.CYP2C92/CYP2C917
D.CYP2C917/CYP2C917
E.None of the above

B.CYP2C92/CYP2C92

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Which CYP2C9 genotype requires a high dose of warfarin?
A.CYP2C91/CYP2C91
B.CYP2C92/CYP2C92
C.CYP2C92/CYP2C917
D.CYP2C917/CYP2C917
E.None of the above

D.CYP2C917/CYP2C917

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Which of the following genes is associated with metoprolol bradycardia and dizziness?
A.CYP2C9
B.CYP2D6
C.CYP3A
D.CYP4F2
E.None of the above

B.CYP2D6

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Which one of the following CYP2D6 phenotypes would be associated with metoprolol bradycardia and dizziness??
A.Ultrarapid metabolizer
B.Normal metabolizer
C.Intermediate metabolizer
D.Poor metabolizer
E.None of the above

D.Poor metabolizer

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Which one of the following CYP2D6 genotypes is associated with poor metabolism?
A.CYP2D61/CYP2D62
B.CYP2D62/CYP2D63
C.CYP2D63/CYP2D64
D.All of the above
E.None of the above

C.CYP2D63/CYP2D64

The CYP2D6*2, *33, and *35 alleles are also considered to confer normal activity.

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In an intermediate CYP2D6 metabolizer of metoprolol with related symptoms, what would be the best clinical care?
A.Continuing monitoring
B.Decreasing the metoprolol dose
C.Increasing the metoprolol dose
D.Switching to another β blocker
E.None of the above

B.Decreasing the metoprolol dose

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Which CYP2D6 diplotype is an ultra metabolizer?
A.CYP2D61×2/CYP2D62
B.CYP2D62×2/CYP2D63
C.CYP2D63×2/CYP2D64
D.CYP2D64×2/CYP2D65
E.None of the above

A.CYP2D61×2/CYP2D62

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Which gene is associated with codeine toxicity?
A.CYP2C9
B.CYP2D6
C.CYP3A
D.VKORC1
E.None of the above 1

B.CYP2D6

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Which phenotype would be associated with codeine toxicity?
A.Ultrarapid metabolizer
B.Normal metabolizer
C.Intermediate metabolizer
D.Poor metabolizer
E.None of the above

A.Ultrarapid metabolizer

Codeine is a prodrug

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What allele is associated with allopurinol-induced severe cutnaeous adverse reactions (SCAR)?
A.HLA-A31:01
B.HLA-B15:02
C.HLA-B57:01
D.HLA-B58:01
E.None of the above

D.HLA-B*58:01

Most commonly in Asians

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CYP2D6 genotype associated with codeine toxicity?
A.CYP2D61×3
B.CYP2D64×4
C.CYP2D610×2
D.CYP2D617×1
E. None of the above

A.CYP2D6*1×3

Codeine is a prodrug

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Which CYP2D6 phenotype is associated with risperidone toxicity?
A.Ultrarapid metabolizer
B.Normal metabolizer
C.Intermediate metabolizer
D.Poor metabolizer
E.None of the above

D.Poor metabolizer

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Which one of the following medications would most likely cause adverse effects in a CYP2D63/5 genotype?
A.Aripiprazole
B.Carbamazepine
C.Divalproex
D.Lamotrigine
E.None of the above

A.Aripiprazole

Which allele is associated with risperidone metabolism?
A.CYP2B6
B.CYP2C9
C.CYP2D6
D.CYP3A
E.None of the above

C.CYP2D6

risperidone has been the most commonly prescribed antipsychotic
prodrug
less extent by CYP3A4

Which one of the following alleles most likely is associated with high risk for carbamazepine-induced hypersensitivity reactions? A. HLA-B*15:02 B. HLA-B*15:11 C. HLA-B*57:01 D. HLA-B*58:01 E. None of the above

A. HLA-B*15:02 SE Asians

Which one of the following populations has the highest carrier frequency for HLA-B*15:02? A. African American B. Asian C. Caucasian D. Hispanic E. None of the above

B. Asian

What is the proper medical decision for a patient with carbamazepine hypersensitivity (MPE, SJS, TEN, DRESS)? A. Continuing monitoring B. Decreasing the dose C. Increasing the dose D. Using an alternative drug E. None of the above

D. Using an alternative drug

Which of the following alleles is associated with phenytoin associated SJS? A. HLA-B*15:02 B. HLA-B*15:11 C. HLA-B*57:01 D. HLA-B*58:01 E. None of the above

A. HLA-B*15:02 HLA-A*31:01 with carbamazepine HLA-B*15:11linked with carbamazepine-induced SJS/TEN HLA-B*57:01 hypersensitivity reactions with abacavir (ABC) HLA-B*58:01 (SCAR) during treatment with allopurinol

The patient is homozygous for HLA-B*15:02 and has skin rashes with seizures controlled by CBZ and PHT. What is the best clinical decision? A. Continuing CBZ B. Switching to PHT or carbamazepine with increased dose C. Switching to PHT or carbamazepine with decreased dose D. Using an alternative drug E. None of the above

D. Using an alternative drug

Which of the following genes may also affect PHT metabolism? A. CYP2C9 B. CYP2C19 C. CYP2D6 D. CYP3A E. None of the above

A. CYP2C9

PHT-induced SJS with compound heterozygous for HLA-B*3701/B*4601 and homozygous for CYP2C9*2/*2 (poor metabolizer). What is the best clinical decision? A. Continue monitoring B. Decreasing the PHT dose C. Increasing the PHT dose D. Using an alternative drug E. None of the above

B. Decreasing the PHT dose

Which gene is associated with clopidogrel metabolism? A. CYP2C9 B. CYP2C19 C. CYP2D6 D. CYP3A E. None of the above

B. CYP2C19

Which of the following CYP2C19 diplotypes is associated with recurrent thrombus with clopidogrel? A. CYP2C19*1/*1 B. CYP2C19*2/*2 C. CYP2C19*3/*3 D. CYP2C19*4/*4

B. CYP2C19*2/*2

Which of the following melanoma genes would be associated with TKI inhibitors such as dabrafenib or vemurafenib? A. BRAF B. EGFR C. KRAS D. NRAS E. None of the above

A. BRAF

What is the correct clinical actions given a patient with a CYP2C19*2/*3 diplotype? A. Continuing monitoring B. Reducing the clopidogrel dose C. Increasing the clopidogrel dose D. Using an alternative drug E. None of the above

D. Using an alternative drug

Which one of the following CYP2C19 alleles contains a variant at the noncoding region? A. CYP2C19*1 B. CYP2C19*2 C. CYP2C19*3 D. CYP2C19*17 E. None of the above

D. CYP2C19*17 c.-806C>T promoter and ultrarapid metabolizer

Which of the following genes would most likely affect 5FU treatment? A. CYP2D6 B. DPYD C. HLA-B*15:02 D. VKORC1 E. None of the above

B. DPYD

What variant would be most likely in melanoma? A. BRAF V600D B. BRAF V600E C. BRAF V600K D. BRAF V600R E. None of the above

B. BRAF V600E

Which gene allele is associated with 5FU toxicity? A. DPYD*1 B. DPYD*2A C. DPYD*4 D. DPYD*9A E. None of the above

B. DPYD*2A DPYD*2A, DPYD*13 are non-functional

Which gene is associated with IROX (irinotecan and oxaliplatin) treatment for COADREAD? A. CYP2D6 B. DPYD C. HLA-B*15:02 D. UGT1A1 E. None of the above

D. UGT1A1

Given a DPYD*2A/*2A diplotype and COAD with discussion of 5FU treatment, what would be the appropriate clinical decision? A. Continue monitoring B. Decreasing the 5-FU dose C. Increasing the 5-FU dose D. Using an alternative drug E. None of the above

D. Using an alternative drug

Given 5FU treatment with toxicity , subsequent testing showing UGT1A1*28. and discussion of treatment change to irinotecan, what is the best clinical decision? A. Continuing monitoring B. Reducing the irinotecan dose C. Increasing the irinotecan dose D. Using an alternative drug E. None of the above

B. Reducing the irinotecan dose

Which gene is associated with gentamicin ototoxicity? A. CYP2D6 B. DPYD C. HLA-B*15:02 D. MTRNR1 E. None of the above

D. MTRNR1 m.1555A>G)

Which of the following genes is associated with azathioprine-induced myelosuppression? A. DPYD B. HLA-B*15:02 C. MTRNR1 D. TPMT E. None of the above

D. TPMT AZT is a prodrug Thiopurine S-methyltransferase

Which of the following diplotypes is associated with low TPMT activity? A. TPMT*1/*1 B. TPMT*1/*2 C. TPMT*3A/*3A D. TPMT*1/*3A E. None of the above 4

C. TPMT*3A/*3A Three variant TPMT alleles account for over 90% of the reduced or absent activity TPMT alleles. They are TPMT*2 (c.238G>C), TPMT*3A (c.460G>A and c.719A>G), TPMT*3B (c.460G>A), and TPMT*3C (c.719A>G).

Given a proven TPMT*2/*3A diplotype, what is the most appropriate clinical decision with AZT treatment? A. Continuing monitoring B. Administering a reduced dose C. Administering an increased dose D. Using an alternative drug E. None of the above

D. Using an alternative drug

Which gene is associated with statin-induced myopathy? A. DPYD B. HLA-B*15:02 C. MTRNR1 D. SLCO1B1 E. None of the above

D. SLCO1B1

Given a homozygous CC in the SLC01B1 gene, what is the most appropriate clinical decision? A. Continuing monitoring B. Administering a reduced dose C. Administering an increased dose D. Using an alternative drug E. None of the above

B. Administering a reduced dose

Which drug may inhibit CYP2C19 and exacerbate an intermediate metabolizer (CYP2C19*1/*2)?

PPI (omeprazole) but not Protonix (pantoprazole)

Clopidogrel is A. A gpIIb/IIIa inhibitor B. A postdrug C. A prodrug D. A thrombin inhibitor E. Inactivated by CYP2C19*17 alleles

C. A prodrug

What percentage of AA are expected to be poor metabolizers of clopidogrel? A. <1% B. 3-5% C. 10-20%. D. 20-30% E. 30-40%

B. 3-5%

CYP2C19*2 and CYP2C19*3 allelic variants: A. Are deletions B. Are detected by protein assays C. Are gene duplications D. Are point mutations E. Can show normal enzyme activity

D. Are point mutations

The CYP2C19*17 allele is associated with A. Decreased clopidogrel active metabolite levels B. Increased clopidogrel prodrug levels C. Increased CYP2C19 protein production D. Increased risk of thrombosis E. Intermediate metabolism of clopidogrel

C. Increased CYP2C19 protein production Mutation is in the 5' UTR promoter, increased bleeding risk

The CYP2C19*3 allele: A. Causes thrombocytopenia in patients on clopidogrel B. Causes thrombocytopenia in patients on prasugrel C. Is associated with variability in ABCB1 D. Is less frequent than the *17 allele E. Is more frequent than the *2 allele

D. Is less frequent than the *17 allele *ABCB1 also associated with decreased response to clopidogrel

Does the rare CYP2C19*10 variant interfere in the CYP2C19*2 TaqMan assay?

Yes CYP2C19*10 variant (g.19153C>T) is due to a single base change in the nucleotide just upstream of the CYP2C19*2 variant (g.19154G >A). This prevents hybridization of the probes used in the CYP2C19*2 assay. Thus, rare patients who are CYP2C19*2/*10 compound heterozygous (less than 1% of the population) will be misclassified as CYP2C19*2/*2. Because the *10 allele is rare and has significantly reduced enzymatic activity, compared to the *2 allele which has no enzymatic activity, misidentification of CYP2C19*2/*10 patients as CYP2C19*2/*2 has minor clinical implications for clopidogrel response.