Phase II pharmacogenetics Flashcards
What are the three polys of GST and their impact
GSTM1 - loss of activity
GSTT1 - loss of activity
GSTP1 - small change in catalytic activity
How many people lack GSTM1
50% white europeans
Molecular basis of GSTM1 poly
Homozygous for a large deletion
How many people lack GSTT1
0 to 20% caucasians
due to a deletion
How are slow acetylators identified
Isoniazid
NAT2 common variant alleles
*5, *6, *7 - slow acetylation
*5 is low activity
*6 and *7 is practically no activity
Frequency of slow acetylators
50% europeans
What is caused by UGT1A1 poly
Gilbert’s syndrome
Caused by higher than normal plasma bilirubin (bilirubin is metabolised by UGT1A1)
UGT2B7 poly molecular basis
His to Tyr substitution
Has linkage disequilibrium to C to T poly close to promoter region
(TT associated with increased morphine glucuronidation)
Where is the most common SULT poly
SULT1A1
What are the two SULT1A1 polys
Copy number variation
3-UTR - regulation by miRNA
What is the 3-UTR
3’ untranslated region
comes right after the stop codon
it contains binding sites for regulatory proteins and miRNAs
What does miRNA binding do in the 3’UTR
Reduced gene expression by inhibiting translation or by mRNA cleavage
What are the two thiopurine methyl transferase polys
*2 - less common - Ala to Pro
*3 - more complex - Ala to Thr & Tyr to Cys
Both causes loss of activity
Why is it important to genotype individuals before cancer treatment
Cancer treatment uses 6- mercaptopurine which is methylated by TPMT so they need to be screened for autoimmune diseases
