Pharmacogenomics

Question 1

Main factors that can affect the genetic variability of the drug response (8)

Answer 1

Age
Gender
Pregnancy
Dietary factors
Body weight
Environment
Underlying disease
Drug interactions

Question 2

Polymorphisms in CYP2C9 and their relation to warfarin

Answer 2

Accounts for 15-20% of metabolism, including warfarin. CYP2C9*2 and 3 are reduced-function variants, and 2C915 and *25 are null variants. Null variants need close monitoring due to high incidence of bleeding events.

Question 3

Common VKORC1 SNP and warfarin

Answer 3

VKORC1 is a direct target of warfarin with a common polymorphism of the promoter region (-1639G>A). This SNP has low VKORC1 expression, so those with that need a lower dose

Question 4

Breakdown of ethnic differences in VKORC1 -1639G>A

Answer 4

37% whites
14% Africans
90% Asians

Question 5

Other considerations of VKORC1 SNPs

Answer 5

Some other really rare mutations in the coding region are associated with resistance that requires very high doses of warfarin to achieve anticoagulation

Question 6

Barriers of full implementation of pharmacogenomics into clinical practice

Answer 6

Physician education
No data demonstrating utility
Lack of evidence for added value above current practice
Availability of alternative medications
Cost effectiveness
Lack of reimbursement
Lack of clear clinical guidelines

Question 7

Targeted therapy

Answer 7

Used mostly in the treatment of cancers; specific molecular target is found based on unique mutations or genetics.