Pharmacogenetics

Question 1

ALDH2*2

Answer 1

an inactive variant of the allele for acetaldehyde dehydrogenase. Prevalence of this SNP is 40% in Asians- cause of “Asian flush”. Same as effect of Disulfiram (ALDH inhibitor).

Question 2

Genetic information nondiscrimination act (GINA) of 2008

Answer 2

stipulates non-discrimination on the basis of genetic information by health insurers and employers (ONLY).

Question 3

How are mono and polygenic traits inherited (F2)?

Answer 3

monogenic inheritance pattern will have a bi or tri-modal distribution- one peak for each possible phenotype.

polygenic inheritance pattern will have a wide, unimodal distribution.

Question 4

Thiopurine-S-methyltransferase (TPMT)

Answer 4

Enzyme responsible for metabolizing (inactivating) 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). TPMT*3A has 2 SNPs (point mutations) that result in a non-functional protein.

Patients who are heterozygous or 3A/3A require a LOWER dose to avoid aplastic anemia.

Question 5

Dihydropurine dehydrogenase (DPD)

Answer 5

Responsible for metabolizing/inactivating 5-Fluorouracil (5-FU) (prescribed for solid tumors). There is a SNP in this gene that can cause deletion of an exon and create a non-functional protein. This results in increased drug toxicity.

Question 6

Cyp2D6

Answer 6

Can metabolize 25% of drugs. Responsible for 50% of ADRs. Several SNPs have been identified that create a full-range of response types from Ultra to poor metabolizers.
CYP2D61 is WT
CYP2D62xN indicates repeat sequences and increased (Ultra) metabolizer type
CYP2D6*N indicates a poor metabolizer type.

Question 7

pharmacogenomics

Answer 7

study of all genetic variants/polymorphisms that influence a patient’s response to a drug. GENOTYPE driven. Genome is sequenced and compared to a database of SNPs that are associated with drug response phenotypes.

Question 8

Pharmacogenetics

Answer 8

The process of identifying SNPs for unusual or adverse drug responses beginning with the observation of the phenotype. Process is: ID response; determine if trait is monogenic or polygenic; if monogenic, conduct family studies to determine inheritance pattern; ID genes; sequence genes for SNPs that confer ADR phenotype.
Limitation: only a limited number of drug responses are monogenic.