Module 4: Pharmacogenetics & Pharmacogenomics

Question 1

Polymorphism

Answer 1

Variability of a particular gentoype that leads to the various expression of observed phenotypes

the spectrum of variations in one genotype that can lead to different phenotypes

Question 2

Copy Number Variations

Answer 2

• type of polymorphism
• Deletion/duplication of 1Kb or larger of DNA fragments
• disease susceptibility
• ability to adapt to the surrounding environment
• BIG changes

Question 3

Single Nucleotide Polymorphisms

Answer 3

• type of polymorphism
• most common type
• very small variation–on the scale of one single nucleotide
• associated with drug responses or susceptibility to develop diseases

Question 4

CPIC

Answer 4

• Clinical Pharmacogenetics Implementation Consortium
• provides evidence-based, genotype-based drug guidelines
• Level A and B will give you actionable recommendations
• Level C and D are not fully supported by Data
  
  • may not have recommendations

Question 5

PharmGKB

Answer 5

Pharmacogenomics Knowledgebase

• classify genomic variation
• FDA approved
• Level 1 = High level of Evidence
• Level 4 = unsupported
  
  • some reported variation of the gene but without the supporting data

Question 6

Variations of CYP2C9 and Warfarin

Answer 6

• variations of CYP2C9 impair warfarin metabolism
  
  • leads to increased levels of warfarin

Question 7

VKORC1 gene and warfarin

Answer 7

• VKOR = enzyme that reduces vitamin K to be able to do its job
• variations in the VKORC1 gene interfere with the VKOR
  
  • this leads to increased anti-coagulation
  • must reduce dose of warfarin if pt’s have these genes
    
    • Warfarin inhibits VKOR

Question 8

Phenoconversion

Answer 8

• a mismatch of genotype-phenotype
  
  • converts genotypic extensive metabolizers (EMs) into phenotypic poor metabolizers (PMs)
• many drugs can induce phenoconversion
  
  • enzyme inducer and inhibitor can cause phenoconversion

Question 9

Solute Carrier Transporter

Answer 9

• aka SLC
• Both influx and efflux activities
• protein
• 3 types:
  
  • Organic Anion Transporter (OAT)
  • Organic Anion Transporting Polypeptides (OATP)
    
    • only influx transporters
  • Organic Cation Transporter (OCT)

Question 10

Organic Anion Transporting Polypeptides

Answer 10

Type of SLC (Solute Carrier Transporter)

is only an influx transporter (not an efflux transporter)