Pharmacogenomics

Question 1

Gene definition

Answer 1

Sequence of nucleotides that code for a SINGLE PROTEIN

Question 2

Allele definition

Answer 2

The specific form a a gene

Wild type - most commonly occurring

Question 3

Genotype definition

Answer 3

Unique genes that determine a specific trait

Ex: homozygous recessive

Question 4

Phenotype definition

Answer 4

Outward expression of the genotype

Ex: hair color

Question 5

Single nucleotide polymorphism (SNP) definition

Answer 5

change in a SINGLE nucleotide
Most common genetic alteration in DNA
Responsible for the majority of individual variability in response to a drug

Question 6

What genetic testing should be done in someone starting abacavir? What do positive/negative results mean?

Answer 6

HLA-B*5701
Positive - risk of hypersensitivity reaction
Do NOT use in positive patients

Question 7

What genetic testing should be done in someone starting Allopurinol (Zyloprim, Aloprim)? What do positive/negative results mean?

Answer 7

HLA-B*5801
Positive - increased risk of SJS
Do NOT use in positive patients

Question 8

What genetic testing should be done in someone starting Carbamazepine, Oxcarbazepine, Phenytoin, Fosphenytoin? What do positive/negative results mean?

Answer 8

HLA-B*1502
Positive - increased risk of SJS
Do NOT use in positive patients
ALWAYS test Asian patients

Question 9

What genetic testing should be done in someone starting clopidogrel (Plavix)? What do positive/negative results mean?

Answer 9

CYP2C19
*2 and *3 alleles indicate poor metabolizers
Clopidogel is prodrug so pt will get decreased effect - consider alternative therapy

Question 10

What genetic testing should be done in someone starting codeine? What do positive/negative results mean?

Answer 10

CYP2D6
Ultra-rapid metabolizers are at increased risk of overdose (Codeine is prodrug converted to morphine)
If ultra-rapid metabolizer - do not use, especially in nursing mothers

Question 11

What genetic testing should be done in someone starting warfarin? What do positive/negative results mean?

Answer 11

CYP2C19*2 and *3 and VKORC1
Positive = increased bleeding risk
Start at lower dose

Question 12

What genetic testing should be done in someone starting Trastuzumab (Herceptin)? What do positive/negative results mean?

Answer 12

HER2 expression

If positive can use trastuzumab - if negative pt will not receive benefit from trastuzumab

Question 13

What genetic testing should be done in someone starting Cetuximab (Erbitux)? What do positive/negative results mean?

Answer 13

KRAS mutation

Only use if KRAS negative - if positive pt will not receive benefit

Question 14

What genetic testing should be done in someone starting azathioprine? What do positive/negative results mean?

Answer 14

Thiopurine methyltranserase (TPMT)
Low/absent TPMT activity increases risk of myelosuppression
If TPMT activity is low/absent start at very low dose or use alternative treatment

Question 15

What genetic testing should be done in someone starting capecitabine (Xeloda) and Fluorouracil? What do positive/negative results mean?

Answer 15

DPD deficiency
DPD deficiency increases risk of severe toxicity
If DPD present, do not use

Question 16

What drugs require/strongly recommend genetic testing?

Answer 16

Abacavir and any combination products containing abacavir
Azathioprine
Carbamazepine
Cetuximab and other EGFR inhibitors
Trastuzumab and other HER2 inhibitors