CYP450s Flashcards
Most common CYP2D6 polys in Europe?
*3, *4, *5
Clinical consequence of CYP2D6 lack of activity
Patients suffered hypotension when given debrisoquine
CYP2D6*4 molecular basis
Splicing defect. Truncated protein & premature stop codon
CYPD2D6*3 molecular basis
Deletion –> Frameshift. Premature stop codon
CYP2D6*5 molecular basis
CYP2D6 deleted
Poor metabolisers are heterozygous for
CYP2D6*4
CYP2C19 has polys involved in metabolism of
Mephenytoin
Most common CYP2C19 poly in UK
CYP2C19*2
Most common CYP2C19 poly in East asia
CYP2C19*3
CYP2C19*2 molecular basis
Splicing defect - absence of activity
AT is normal but GA in *2 is spliced more efficiently
CYP2C19*3 molecular basis
Immediate stop codon - absence of activity
CYP2C19*17 molecular basis
Poly in upstream control sequence
C to T
Increased activity due to more gene txn
Most common CYP2A6 poly in Europe
CYP2A6*2 - No haem incorporated - decreased activity
Most common CYP2A6 poly in East asia
CYP2A6*4 - large deletion - no enzyme
Most common CYP2C9 poly
CYP2C9*2 - Arg144Cys - reduced activity
Most detrimental CYP2C9 poly
CYP2C9*3 - Ile359Leu
What substrates metabolism is affected by CYP2C9’s polys
Warfarin
CYP3A4 polys (most common)
*2 and *22
CYP3A4*2 molecular basis
Ser222Pro - slightly less efficient nifedipine metabolism
CYP3A4*22 molecular basis
Intronic polymorphism
C to T in exon 6
lower mRNA levels
CYP3A5 poly & molecular basis
*3 - splicing defect - nonsense protein - loss of activity
What is the PXR
CYP3A4 txn regulator
What are the PXR polys
Upstream
C to T
G to A
Always seen together due to linkage disequilibrium
When is the most activity seen in the PXR
When it has T instead of C
What is the main poly associated with CYP1A1
A greater ability to induce CYP1A1 induction mediated by AhR
Most significant CYP1A2 SNP
Within promoter region - CYP1A2*1F
