Wk 17: Pharmacogenomics

Question 1

What is the definition of pharmacogenetics?

Answer 1

Study of single gene-drug interaction

Question 2

What is the definition of pharmacogemonics?

Answer 2

Study of complex relationships btw genome + drug response

Question 3

What technologies are used in pharmacogenomics?

Answer 3

• Single nucleotide variant arrays: single base change
• Microarray gene chips: panels of many genes
• Quantitative polymerase chain reactions: single gene
• DNA sequencing: mutational analysis
• Next generation sequencing: whole genome

Question 4

How does microarray probes work?

Answer 4

• Take Patients DNA
• Add biotin
• If it matches it hybridizes
• Conjugate fluorescent molecule is added

Question 5

What is used to handle large gene databasets?

Answer 5

Bioinformatics

Question 6

What is an example of the use of pharmacogenomics to identify patients who will respond to a drug?

Answer 6

Herceptin (breast cancer)

Question 7

What is an example of the use of pharmacogenomics to identify patient drug metabolism?

Answer 7

• Tamoxifen (breast cancer)
• 6-mercaptopurine (leukaemia)
• Warfarin

Question 8

What is an example of the use of pharmacogenomics to predict adverse reactions?

Answer 8

Abacavir (HIV)

Question 9

What is CYP450?

Answer 9

• Key drug metabolisers
• Expressed in liver
• Genetic variant affect efficacy, influencing ADME

Question 10

What is tamoxifen metabolised to?

Answer 10

4 hydroxy TAM by CYP

Question 11

What reduces the efficacy of tamoxifen?

Answer 11

Variants of CYP2D6

Question 12

What produces the highest level of metabolism?

Answer 12

2 functional alleles - inc mRNA -> higher enzyme level

Question 13

Which ethnicity are intermediate metabolisers of tamoxifen?

Answer 13

Asians (30%)