Pharmacogenomics

Question 1

What did the human genome project find?

Answer 1

>99% of nucleotide bases are the same in all humans

we have 3 billion bases

Note: the differences are mostly SNP variations

Question 2

VKORC1 polymorphism (G1639A)

Answer 2

lower levels of VKORC1

this implies we need less warfarin in the system since there is less enzyme to be inhibited

Question 3

NAT2 - implication of having just protein coding region

Answer 3

having no introns, if something is wrong with this it will be more likely to cause a mutation cause there are no piece of it that are left out

Question 4

coding region vs non-coding region

Answer 4

Coding region is more likely to cause a mutation, in the non coding region it is not expressed

Non-coding SNPs can change the way a gene is regulated or its stability

Question 5

Which are pro drugs?

Warfarin, Codeine, Clopidogrel, Tamoxifen, Vemurafenib?

Answer 5

Codeine

Clopidogrel

Tamoxifen

Question 6

G6DP deficiency

Answer 6

hemolysis

it normally protects agains ROS -> deficiancy = early RBC death

Question 7

BChE heredity

Answer 7

autosomal recessive

Question 8

CYP2D6 and tamoxifen

Answer 8

deficiency = less active metabolite

active metabolites = more affinity at the estrogen receptor

(breast cancer drug)

Question 9

BChE deficiency

Answer 9

slow break down of Succs → longer apnea time

Question 10

warfarin and vit K Epoxide Reductase

Answer 10

Epoxide Reductase is the enzyme targeted by warfarin

coumadin inhibits it → less clotting happening

Question 11

What metabolizes Codeine?

Answer 11

CYP2D6

Question 12

what metabolizes Clopidogrel

Answer 12

CYP2C19

Question 13

G6PD heredity

Answer 13

X- linked recessive pattern

male are more likely to be affected (only one X)

son of a dude with this deficiency could be just a carrier if the mom doesn’t have the deficiency

Question 14

VKORC1 - role?

Answer 14

Vit K Epoxide Reductase

reduces vit k (makes it in the form needed to catalyze the formation of the clotting factor 2, 7, 9, 10)

Question 15

cons of pharmacogenomics

Answer 15

1. genetics is only a small piece of the big picture
2. false positives
3. cost
   
   • it’s expensive
   • benefits a minority of ppl
   • sometimes more costly than dealing with adverse drug reactions
4. delayed results and treatment
   
   • when someone is sick they want immediate results

Question 16

vemurafenib

Answer 16

targets a mutation in a specific proto-oncogene (BRAF) type - the V600E type

Question 17

what metabolized Tamoxifen?

Answer 17

CYP2D6

Question 18

NAT2 deficiency - effects

Answer 18

Isonizaid is not metabolized and pt’s suffer from toxicity to the drug (neuropathy etc)

Question 19

NAT2 deficiency - general picture

Answer 19

acetylation polymorphism

not a SNP cause it has 2-3 point mutations

Question 20

CYP2D6 and codeine metabolism

Answer 20

turns Codeine into morphine

low metabolizers = no effects; no pain relief

high metabolizers = morphine intoxication, respiratory depression

Question 21

CYP2C19 polymorphism

Answer 21

1. *1 = normal metabolism of clopidogrel = there will be active metabolites to inhibit ADP on platelets
2. *2 = no metabolism of clopidogrel = no active metabolite to do the work
   
   • most common
3. *3 = no metabolism
   
   • less common
4. *17 = fast metabolism

Question 22

pros of pharmacogenomics

Answer 22

1. increases efficiency
2. reduces toxicity
3. reduces hospitalizations related to adverse drug reactions
4. gemone sequence is a one in a life time test that allows for personalized care for the rest of one’s life

Question 23

CYP2C9 and metabolism of __ drug

*1

*2

*3

Answer 23

*1 (wild type) = normal metabolism of warfarin

*2 = 30% slower metabolism of warfarin

*3 = 90% slower

• need the lowest dose

Question 24

Who metabolized Warfarin?

Answer 24

CYP2C9

metabolizes S-warfarin; X5 more potent than R-warfarin

Question 25

SNP is…

SNP is NOT ..

Answer 25

Single nucleotide polymorphism is a DNA sequence variation that occurs when a single nucleotide (A, T, C, or G) in the genome is altered

SNP is not the same as disease-causing mutation, and the majority of SNPs are in non-coding regions.