pharmacogenetics lect 9

Question 1

neutral mutation

Answer 1

changes the amino acid sequence of a protein without altering its ability to function

Ex: acidic amino acid is replaced with another acidic amino acid

Question 2

90% of all human genetic variation comes from what

Answer 2

SNPs

Question 3

missense mutation

Answer 3

a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid

Question 4

nonsense mutation

Answer 4

a point mutation in a sequence of DNA that results in a premature stop codon

Question 5

what are pharmacogenetically-important mutations

Answer 5

any mutation that

• changes gene copy number (gene duplication or deletion)
• changes function of the protein
• can have pharmacological consequences

Question 6

what is an example of a change in protein function

Answer 6

NAT2

Question 7

what is the function of NAT2

Answer 7

• Transfers an acetyl group from acetyl-CoA to the acceptor amine resulting in formation of an amide on the drug.

Question 8

NAT2 is Involved in the metabolism of the following drugs:

Answer 8

Isoniazid, hydralazine, procainamide

**Genetic variation in NAT2 results in striking differences in the half-life and plasma concentrations of drugs metabolized by NAT2

Question 9

a single isozymic variant of the NAT creates what two divisions of liver metabolism

Answer 9

fast and slow Acetylators

*individuals are identified as a rapid or slow acetylator by determining plasma concentration of a test drug (such as isoniazid) at a specified time after administering a fixed dose

Question 10

Phenotypic slow acetylators have what alleles

Answer 10

rr

Question 11

Phenotypic rapid acetylators have what alleles

Answer 11

may be either homozygous or heterozygous for the rapid allele (R/R or R/r)

*rapid allele is dominant

Question 12

Adverse effects are related to the rate of acetylation of the drugs procainamide, hydralzaine via the slow allele (slow NAT activity) gives rise to what disease

Answer 12

Lupus

*slow rate of acetylation means drug is around longer in the body

Question 13

Adverse effects are related to the rate of acetylation of isoniazid via the rapid allele (rapid NAT activity) gives rise to what condition

Answer 13

hepatotoxicity

Question 14

what is a gene copy number example

Answer 14

CYP2D6

Question 15

what is the first and second most common metabolizing enzyme

Answer 15

1. CYP3A4
2. CYP2D6
   
   1. ​has >90 alleles that will make a patient be a
      
      1. poor metabolizer
      2. intermediate metabolizer
      3. (extensive) normal metabolizer
      4. ultrarapid metabolizer

Question 16

CYP2D6 is involved in the metabolism of the following drugs:

Answer 16

codeine. fluoxetine, oxycodone, tricyclic antidepressants

Question 17

what are microarrays

Answer 17

“gene chips”

• have the ability to measure gene expression level
• identify alleles

Question 18

name two current microarrays

Answer 18

1. roche amplichip: looks at gene variations in CYP2D6 and CYP2C19 genes
2. Affymetrix DMET plus panel