Pharmacogenomics

Question 1

Pharmacogenetics

Answer 1

study of the genetic basis for variations in drug

response. Typical used to define the study of how variation in single gene influences the response to a single drug

Question 2

Pharmacogenomics

Answer 2

study of how all of the genes (the genome) can

influence responses to drugs

Question 3

Monogenic drug response

Answer 3

Variation in a single gene causing difference in specific drug response

Question 4

Multigenic drug response

Answer 4

Variations in multiple genes causing difference in a specific drug response

Question 5

Gene by environment phenotype

Answer 5

Drug response is a complex interplay between environmental and genetic factors

Question 6

Mutation

Answer 6

Difference in DNA code that occurs in less than 1% of the population

Question 7

Polymorphism

Answer 7

Difference in DNA code that occurs in more than 1% of the population

Question 8

Allele

Answer 8

one of a number of alternate forms of a gene

Question 9

SNP =

Answer 9

single nucleotide change in protein coding region

Question 10

Synonymous SNP

Answer 10

NUCLEOTIDE CHANGE DOES NOT CAUSE AMINO ACID SUBSTITUTION

Question 11

Non-synonymous SNP

Answer 11

LEADS TO AN AMINO ACID SUBSTITUTION

Question 12

Indel

Answer 12

insertions/deletions

addition or loss of genetic material

can lead to frameshift - change AA or insert stop codon

alter promoter or enhancer - can increase transcription quantity

Question 13

Most SNP’s are found

Answer 13

in regions that are NON-PROTEIN CODING REGIONS (enhancers, promoters, introns)

Question 14

Copy number variation (CNV)

Answer 14

either complete deletion or duplication of a particular gene

gain or loss of function results

Question 15

Cosmopolitan polymorphisms

Answer 15

polymorphisms common across all ethnic groups

Question 16

Population polymorphisms

Answer 16

polymorphisms that differ between groups (ethnic or race)

Question 17

Phenotype to genotype approach

Answer 17

start out BY DIRECTLY MEASURING PHARMACOGENETIC TRAIT

Question 18

Pharmacogenetic trait

Answer 18

any measurable trait associated with DRUG ENZYME ACTIVITY, DRUG LEVELS IN BODY, DRUG METABOLITE IN BODY FLUIDS, PHYSIOLOGIC RESPONSE

Question 19

Candidate gene approach

Answer 19

determine polymorphisms by genotyping specific gene predicted to cause differences in pharmacogenetic trait between two groups

REQUIRES KNOWLEDGE OF CELLULAR MECHANISM

WRONG GENE MIGHT BE STUDIED

Question 20

Genome wide approach

Answer 20

DOES NOT REQUIRE KNOWLEDGE OF CELLULAR MECHANISM RESPONSIBLE FOR TRAIT

UNBIASED SURVEY OF ALL DIFFERENCE IN ENTIRE GENOME BETWEEN TWO GROUPS

identification that does not matter is disadvantage

Question 21

Three types of genome wide approach

Answer 21

sanger sequencing

SNP microarrays

Next generation sequencing

Question 22

4 polymorphisms of CYP2D6

Answer 22

ultra metabolizers
extensive metabolizers
intermediate metabolizers
poor metabolizers

Question 23

CYP2D6 metabolism (3 drugs) (pharmacodynamic or pharmacokinetic?)

Answer 23

tamoxifen
codeine
paroxetine

all three pharmacokinetic

Question 24

CYP2C19 metabolism (3 drugs)

Answer 24

Clopidogrel
Omeprazole
Lansoprazole

Question 25

CYP2C19 levels of metabolism (3)

Answer 25

normal intermediate poor

Question 26

CYP2C9 drug Reduced function alleles?

Answer 26

warfarin CYP2C9*2, CYP2C9*3 -- metabolize slower, lower dose requirements

Question 27

Pharmacokinetic polymorphism of warfarin? Pharmacodynamic polymorphism of warfarin?

Answer 27

CYP2C9 VKORC1

Question 28

VKORC1 SNP with lowest activity?

Answer 28

VKORC1-AA

Question 29

Polymorphisms affecting cancer treatment (2 drugs)

Answer 29

5-FU - DPD and TYMS enzymes 6-MP - TPMT enzyme

Question 30

Role of DPD with 5-FU (pharmacodynamic or pharmacokinetic?) Role of TYMS with 5-FU(pharmacodynamic or pharmacokinetic?)

Answer 30

DPD inactivates 5-FU, REDUCES TOXICITY - DECREASED FUNCTION LEADS TO INCREASED TOXICITY (pharmacokinetic) TYMS is inhibited by 5-FU normally - CAN HAVE INCREASED OR DECREASED ACITIVTY (pharmacodynamic)

Question 31

Role of TPMT with 6-MP

Answer 31

normally INACTIVATES 6-MP

Question 32

SLCO1B1 and Simvastatin (3 levels of function) what chromosome? (pharmacodynamic or pharmacokinetic?)

Answer 32

``` normal transport (T/T genotype) decreased transport (T/C genotype) low transport (C/C genotype) ``` chromosome 12 highly associated pharmacokinetic

Question 33

Estrogen receptor polymorphism | pharmacodynamic or pharmacokinetic?

Answer 33

intron between 1st and 2nd exon of ER-alpha gene homozygotes for less common allele had GREATER INCREASE IN HDL LEVELS FOLLOWING HRT pharmacodynamic

Question 34

ADRB2 phenotype and albuterol use | pharmacodynamic or pharmacokinetic?

Answer 34

ARG/ARG HOMOZYGOTES DECREASED PEF WITH ALBUTEROL ADMINISTRATION passive smoking augments down-regulatory effect pharmacodynamic

Question 35

Indirect pharmacogenetic drug associations (4 drugs)

Answer 35

oral contraceptives abacavir APO-E and alzheimer's drug therapy interferon-alpha and Hep C

Question 36

Polymorphisms in what affect venous thromboembolism with oral contraceptives?

Answer 36

factor V and Prothrombin

Question 37

Abacavir phenotype result?

Answer 37

HLA-B*57:01 HIGH RISK OF HYPERSENSITIVTY REACTION

Question 38

Apo-E phenotype result?

Answer 38

ABSENCE OF CERTAIN ALLELES better therapeutic success for therapy with tacrine in alzheimer's disease

Question 39

SNP polymorphism associated with IFN-alpha effectiveness

Answer 39

IL-28B CC - favorable response genotype CT or TT - unfavorable response genotype