CYP450s

Question 1

Most common CYP2D6 polys in Europe?

Answer 1

*3, *4, *5

Question 2

Clinical consequence of CYP2D6 lack of activity

Answer 2

Patients suffered hypotension when given debrisoquine

Question 3

CYP2D6*4 molecular basis

Answer 3

Splicing defect. Truncated protein & premature stop codon

Question 4

CYPD2D6*3 molecular basis

Answer 4

Deletion –> Frameshift. Premature stop codon

Question 5

CYP2D6*5 molecular basis

Answer 5

CYP2D6 deleted

Question 6

Poor metabolisers are heterozygous for

Answer 6

CYP2D6*4

Question 7

CYP2C19 has polys involved in metabolism of

Answer 7

Mephenytoin

Question 8

Most common CYP2C19 poly in UK

Answer 8

CYP2C19*2

Question 9

Most common CYP2C19 poly in East asia

Answer 9

CYP2C19*3

Question 10

CYP2C19*2 molecular basis

Answer 10

Splicing defect - absence of activity
AT is normal but GA in *2 is spliced more efficiently

Question 11

CYP2C19*3 molecular basis

Answer 11

Immediate stop codon - absence of activity

Question 12

CYP2C19*17 molecular basis

Answer 12

Poly in upstream control sequence
C to T
Increased activity due to more gene txn

Question 13

Most common CYP2A6 poly in Europe

Answer 13

CYP2A6*2 - No haem incorporated - decreased activity

Question 14

Most common CYP2A6 poly in East asia

Answer 14

CYP2A6*4 - large deletion - no enzyme

Question 15

Most common CYP2C9 poly

Answer 15

CYP2C9*2 - Arg144Cys - reduced activity

Question 16

Most detrimental CYP2C9 poly

Answer 16

CYP2C9*3 - Ile359Leu

Question 17

What substrates metabolism is affected by CYP2C9’s polys

Answer 17

Warfarin

Question 18

CYP3A4 polys (most common)

Answer 18

*2 and *22

Question 19

CYP3A4*2 molecular basis

Answer 19

Ser222Pro - slightly less efficient nifedipine metabolism

Question 20

CYP3A4*22 molecular basis

Answer 20

Intronic polymorphism
C to T in exon 6
lower mRNA levels

Question 21

CYP3A5 poly & molecular basis

Answer 21

*3 - splicing defect - nonsense protein - loss of activity

Question 22

What is the PXR

Answer 22

CYP3A4 txn regulator

Question 23

What are the PXR polys

Answer 23

Upstream
C to T
G to A
Always seen together due to linkage disequilibrium

Question 24

When is the most activity seen in the PXR

Answer 24

When it has T instead of C

Question 25

What is the main poly associated with CYP1A1

Answer 25

A greater ability to induce CYP1A1 induction mediated by AhR

Question 26

Most significant CYP1A2 SNP

Answer 26

Within promoter region - CYP1A2*1F