Pharmacogenetics

Question 1

What are the most common type of polymorphisms?

Answer 1

SNPs (nucleotide changes)

Question 2

What is the protein coding gene involved with Isoniazid (INH)

Answer 2

NAT2

Question 3

What is an example of polymorphism involving changes in copy number? Explain this.

Answer 3

CYP2D6 and Nortriptyline
- CYP2D6 metabolizes Nortriptyline but with polymorphisms in CYP2D6, Nortriptyline optimal dose, and occurrence of therapeutic and adverse effects can be altered

Question 4

What is an example of polymorphism involving changes in receptor numbers/function? Explain this.

Answer 4

NAT2 and Isoniazid

- NAT2 acetylates Isoniazid but with polymorphisms in NAT2, Isoniazid half-life and plasma concentration can be altered

Question 5

If someone is a fast acetylator of Isoniazid, what does this mean for enzyme activity and what can this result in?

Answer 5

Fast acetylator: increased NAT2 activity → Hepatotoxicity

Question 6

If someone is a slow acetylator of Isoniazid, what does this mean for enzyme activity and what can this result in?

Answer 6

Slow acetylator: decreased NAT2 activity → Lupus

Question 7

Generally, if enzyme activity is decrease, what will happen to drug metabolism? What will happen to drug concentrations in the plasma?

Answer 7

If enzyme activity is decreased = less metabolism of drug = increased drug concentration in plasma

Question 8

What drug transports statins? What occurs if there is a polymorphism in this transporter?

Answer 8

OATP1B1 is involved in hepatic uptake of drugs (like statins) so they can be excreted from the body
- If there is a mutation, there will be reduced response to statins aka statins are in the serum for longer and active longer to further decrease serum lipids

Question 9

SJS involves what type of immune gene polymorphism? What medication are SJS patients hypersensitive to in this case?

Answer 9

HLA is involved in the immune response, specifically hypersensitivity reactions like SJS
- A mutation in the HLA gene can cause hypersensitivity to Abacavir

Question 10

What medication is associated with CYP2D6 polymorphisms?

Answer 10

Debrisoquin

Question 11

What medication is associated with inhibition of serum cholinesterase?

Answer 11

Dibucaine