General Clinical Genetics

Question 1

A cardiologist is considering starting a patient on clopidogrel. Which of the following pharmacogenetic tests would be most useful to inform this decision?

a. CYP2C19
b. CYP2D6
c. N-acetyl transferase
d. Thiopurine methyltransferase
e. VKORC1

Answer 1

=CYP2C19

this enzyme is required to activate clopidogrel

Question 2

State the goal of each of the 4 phases of a drug trial.

Answer 2

Phase I: maximum tolerated dose and side effects (safety)
Phase II: efficacy
Phase III: compares treatment to alternatives
Phase IV: long-term effects of the drug are monitored

Question 3

Ivacaftor is a CF medication that targets the mutant protein due to a particular mutation by increasing chloride flow through the mutant CFTR. What is the mutation targeted by this medication?

a. 3849 +10kC>T
b. G551D
c. G542X
d. phe508del
e. R117H

Answer 3

=ivacaftor (kaleydico) targets the mutant protein produced by the G551D mutation

the G551D accounts is found in 3-4% of CF patients worldwide

Question 4

HLAB*1502 has been linked to Stevens-Johnson syndrome triggered by what medication?

Answer 4

=carbamazepine

-found especially in the Asian population

Question 5

HLAB*5701 has been linked to hypersensitivity reaction (including Stevens-Johnson syndrome) triggered by what medication?

Answer 5

=abacavir (an anti-retroviral med used in triplet therapy for HIV)

Question 6

Why is TMPT testing performed for patients with leukemia or autoimmune diseases?

Answer 6

TMPT= thiopurine S-methyltransferase

• enzyme involved in inactivation of medications
• low or intermediate activity of this enzyme is associated with increased toxicity and requires lowering the dose

Question 7

What enzyme is involved in codeine metabolism?

a. CYP2C19
b. CYP2D6
c. N-acetyl transferase
d. Thiopurine methyltransferase
e. VKORC1

Answer 7

=CYP2D6

• Codeine converted to morphine by the CYP2D6 enzyme
• A rapid metabolizer would produce too much morphine at a standard dose and may have an overdose type rxn (ex respiratory depression)

Question 8

CYP2D6 is involved in the metabolism of many different medications. All of the following classes of medications are commonly affected by CYP2D6 EXCEPT:

a. analgesics
b. chemotherapy
c. anti-arrhythmics
d. anti-depressants
e. anti-histamines

Answer 8

=b= chemotherapeutics

Question 9

Which of the following enzymes is involved in warfarin metabolism?

a. CYP2D6
b. CYP2C9
c. CYP2C19
d. CYP3A4
e. CYP3A5

Answer 9

=CYP2C9

CYP2C19 involved in conversion of clopidogrel to the active drug

Question 10

N-acetyltransferase 2 is an enzyme involved in drug metabolism. All of the following classes of medications are affected by N-acetyltransferase 2 EXCEPT:

a. antihistamines
b. isoniazid
c. hydralazine
d. chemotherapeutics
e. sulfasalazine

Answer 10

=antihistamines