Pharmacogenomics

Question 1

Process of gene to protein

Answer 1

Promotor on gene, transcription leads to RNA (introns and exons), splicing leads to mRNA (just introns), translation leads to protein

Question 2

Sequences start with ___ and end with stop codon

Answer 2

Methionine

Question 3

SNP is: ____ sequence variation, when a ___ ___ is altered. Must occur in __% of popn. Accounts for, can occur in __ or __

Answer 3

DNA sequence variation when a single nucleotide (a,t,c,g) is altered. Must occur in at least 1% of the popn, accounts for 90% of human genetic variation, can occur in introns or exons

Question 4

SNPs are not the same as __ ___ __ and most SNPs occur in which regions

Answer 4

Disease causing mutations, non-coding regions

Question 5

What happens if SNP in a coding vs non coding region

Answer 5

Coding= changes amino acid

Question 6

G6PD role

Answer 6

Pentose phosphate pathway, provides reducing energy (NADPH) to cells to protect them from ROS

Question 7

G6PD deficiency leads to what

Answer 7

Hemolysis, hemolytic anemia. Broken down faster than body can produce RBCs

Question 8

G6PD inheritance

Answer 8

X linked recessive

Question 9

Males or females more likely to bet G6PD

Answer 9

Males

Question 10

What BChE deficiency leads to

Answer 10

Breaks down sux. If deficient, 1 hr (prolonged) apnea

Question 11

BChE inheritance, prevalence in who

Answer 11

Autosomal recessive. Caucasians, 4% have partial deficiency (5-60 min apnea), 1/2500 have 1+ hr apnea

Question 12

N-acetyltransferase (NAT2) deficiency leads to

Answer 12

Isoniazid- excreted unchanged in urine by slow acetylators- peripheral neuropathy. Metabolism needed to convert isoniazid to acetlisoniazid.

Question 13

NAT 2 deficiency: NAT2 has no what. Variant alleles involve what kind of mutations

Answer 13

Introns, just protein coding regions. 2-3 point mutations

Question 14

NAT2 deficiency occurs mostly in who

Answer 14

40-70% caucasians and African Americans. 10-20% Japanese and Eskimo. 80%+ Egyptians

Question 15

Phase 1 is what

Answer 15

Functionalization reaction. 80% drug metabolized this way

Question 16

Phase 2 is what

Answer 16

Conjugation reaction. Acetylation and glucuronidation (NAT2)

Question 17

Human genome project goals

Answer 17

ID genes, determine human DNA sequence, store info, improve data analysis, transfer technologies to private sector, address ethical/legal issues

Question 18

How many: total bases in genome, bases in average gene, total genes

Answer 18

3 billion bases total. 3,000 bases per gene. 30,000 genes

Question 19

% nucleotides same in all people

Answer 19

> 99%

Question 20

What GINA does

Answer 20

Protects Americans from discrimination based on genetic info in health insurance and employment

Question 21

Warfarin mix: R metabolized by, S metabolized by. Which more potent

Answer 21

R- cyp3a4, 1a2, 1a1. S- CYP2CP. S 5x more potent than R

Question 22

Warfarin inhibits vitamin k ___ ___. Reduced vitamin k is a cofactors for ___ which catalyzes formation of clotting factors.

Answer 22

Epoxide reductase. GGCX

Question 23

Factors that affect balance between preventing clots and preventing warfarin toxicity/coag

Answer 23

Age, BMI, genetics

Question 24

CYP2C9 SNPs do what

Answer 24

Metabolize warfarin. 1- metabolizes normally. 2- reduced metab 30%, 3- reduced metab 90%

Question 25

VKORC1- what it is, ex

Answer 25

Target enzyme for warfarin. Many polymorphisms, G1639A.

Question 26

VKORC1: G/A or A/A variant- lower level VKOR- require _____ dose of warfarin than G/G

Answer 26

G/A OR A/A require lower dose than G/G

Question 27

What contributes to warfarin metabolism: 45%, 25%, 20%, 10%

Answer 27

45- unknown. 25- VKORC1. 20- sex/BMI/age/diet/drugs. 10- CYP2C9

Question 28

MOA clopidogrel

Answer 28

Binds to ADP receptors on plt to prevent aggregation and thrombosis

Question 29

Clopidogrel is a ___ absorbed in ___ and ____ in liver

Answer 29

Prodrug, intestines, activated

Question 30

Clopidogrel: __ __ binds to __ receptor, irreversibly blocking ADP binding and activation

Answer 30

Active metabolite, P2RY12

Question 31

Which plavix variant leads to increased activity

Answer 31

*17 - increased CYP2C19 activity

Question 32

Genetic variants that lead to no CYP2C19 activity, for which drug

Answer 32

Plavix. *2, *3, *4, *5

Question 33

Genetic testing for CYP2C19 variants focuses on which one particularly

Answer 33

*2, higher prevalence

Question 34

Codeine: considered a ____, 10% converted to __ by ___

Answer 34

Prodrug, low affinity for opioid receptors. Prodrug. CYP2D6

Question 35

Codeine: what happens in poor metabolizers vs ultra rapid metabolizers

Answer 35

PM- cant convert drug, no pain relief. Ultra rapid- morphine intoxication, severe respiratory depression

Question 36

Tamoxifen metabolism

Answer 36

Prodrug, converted by CYP2D6. Catalyzes it to metabolites w greater affinity for estrogen receptor.

Question 37

What is vemurafenib

Answer 37

Melanoma drug for BRAF V600E mutations

Question 38

___ mutated in 80% of melanomas

Answer 38

B-raf

Question 39

Drug w strong initial effects then drug resistance leads to recurrence

Answer 39

Vemurafenib

Question 40

Why associations between phenotype and genotype not always reproducible

Answer 40

Diff in study groups, diff end points to study, allergies

Question 41

What pharmacoeconomic model does

Answer 41

Determines if a test is worthwhile to implement. Compares genetic test cost to cost of monitoring pt for ADRs

Question 42

3 early discoveries

Answer 42

G6PD, BChE, NAT-2