Genomics and Individualised Medicine

Question 1

What is the most common cause for genetic variation?

1 - single nucleotide polymorphisms (SNP)
2 - DNA mismatching
3 - mutations in whole gene sequence
4 - mutations in mitochondrial DNA

Answer 1

1 - single nucleotide polymorphisms (SNP
- one nucleotide: A, cytosine, or C, thymine, or T and guanine, or G is changed
- this can affect the structure and function of the protein encoded by the gene

AAGCCTA → AAGCTTA = SNP

Question 2

Single nucleotide polymorphisms (SNP) are the most common causes of genetic variation in humans. Can this have any affect on response to medications?

Answer 2

• yes
• SNPs could determine if the drug is toxic, beneficial and/or ineffective

Question 3

Match pharmacogenetics and pharmacogenomics with the definitions below:

• refers to effects involving a limited number or single genes
• study of complex multigene patterns within the genome

Answer 3

• pharmacogenetics = refers to effects involving a limited number or single genes
• pharmacogenomics = study of complex multigene patterns within the genome

Question 4

Which of the following is NOT a key aspect of pharmacokinetics, which is essentially what the body does to a drug?

1 - Absorption
2 - Distribution
3 - Digestion
4 - Metabolism
5 - Elimination

Answer 4

3 - Digestion

Question 5

Cytochrome P450 is a group of enzymes responsible for metabolising hormones, toxins, drugs etc in the liver. Can this enzyme be affected by genetic variation?

Answer 5

• yes
• genes provide code for proteins and enzymes are proteins

Question 6

Genetic polymorphisms refer to difference in DNA sequence among individuals, groups, or populations, with single nucleotide polymorphisms being the most common. Why is this important in drug metabolism?

1 - drugs can be metabolised faster
2 - drugs can be metabolised slower
3 - drugs may not be metabolised at all
4 - all of the above

Answer 6

4 - all of the above

• people may have different levels or activity of enzymes
• means people metabolise drugs differently

Question 7

If a patient possess a genetic polymorphism causing a duplication of the same allele coding for cytochrome P450, what affect could this have on drug metabolism?

1 - patient would be a extensive metaboliser
2 - patient would be a poor metaboliser
3 - patient would be a ultra rapid metaboliser
4 - patient would be a intermediate metaboliser

Answer 7

3 - patient would be a ultra rapid metaboliser
- form of induction
- drug dose may need to be higher to have same therapeutic effect

Question 8

If a patient possess a genetic polymorphism meaning they have 2 different alleles coding for cytochrome P450, what affect could this have on drug metabolism?

1 - patient would be a extensive metaboliser
2 - patient would be a poor metaboliser
3 - patient would be a ultra rapid metaboliser
4 - patient would be a intermediate metaboliser

Answer 8

1 - patient would be a extensive metaboliser
- normal metabolism occurs
- this is the majority of patients

Question 9

If a patient possess a genetic polymorphism meaning they have one abnormal allele coding for cytochrome P450, what affect could this have on drug metabolism?

1 - patient would be a extensive metaboliser
2 - patient would be a poor metaboliser
3 - patient would be a ultra rapid metaboliser
4 - patient would be a intermediate metaboliser

Answer 9

4 - patient would be a intermediate metaboliser
- slight inhibitor so slower metabolism
- dosage may need to be reduced in order to reduce the risk of adverse events

Question 10

If a patient possess a genetic polymorphism meaning they have 2 abnormal alleles coding for cytochrome P450, what affect could this have on drug metabolism?

1 - patient would be a extensive metaboliser
2 - patient would be a poor metaboliser
3 - patient would be a ultra rapid metaboliser
4 - patient would be a intermediate metaboliser

Answer 10

2 - patient would be a poor metabolise
- form of inhibition on CYP450
- drug metabolism will be slower and could increase toxicity
- dosage may need to be significantly reduced or another drug used

Question 11

The normal allele for europeans for the enzyme cytochrome P450 (CYP450) is CYP29C1. However, Europeans can typically have genetic variations in CYP450, specifically CYP2C92 and CYP2C93, which are associated with reduced enzyme activity. If a patient has 1 or 2 copies of the allele CYP2C92 and CYP2C9*3, what will this mean for the patients drug dose of something like Warfarin, which is dependent on CYP450?

1 - increased dose of warfarin
2 - decreased dose of warfarin
3 - no change in warfarin dose

Answer 11

2 - decreased dose of warfarin
- as the alleles reduce activity of CYP450, the drug could become toxic, so need to lower the dose

Question 12

All nucleated cells in the body posses MHC-I receptors (also called human leukocyte antigens, HLA), which present antigens to T helper and cytotoxic T cells to tell the immune system if the cell is human or infected/damaged. In patients of asian decent, a genetic variation in the Human leukocyte antigens (HLA) B can cause them to have a reaction to a drug that causes Stevens-Johnson syndrome & toxic epidermal necrolysis, an acute immune mediated condition affecting the skin and mucous membranes. Which drug is this associated with?

1 - aspirin
2 - verapamil
3 - carbamazapine
4 - penicillin

Answer 12

3 - carbamazapine
- classed as a type IV hypersensitivity
- had a mortality rate of 30%

Question 13

Which of the following are benefits to sequencing a patients a patients malignant tumours?

1 - more accurate diagnosis and characterisation of tumour
2 - identify any potential receptors/antigens the tumour has
3 - personalised therapy to specific tumours
4 - all of the above

Answer 13

4 - all of the above