ABC & SLCO transporters

Question 1

Three most common ABCB1 polys

Answer 1

Exon 12: Silent C to T
Exon 21: Ala to Ser
Exon 26: Silent C to T

Question 2

What effects to polys in ABCB1 cause

Answer 2

Changes to mRNA and protein expression
Changes to transport activity and substrate specificity
Therefore, reduced transport capacity and reduced drug efflux

Question 3

What effect does haplotype have on cholesterol reduction of statin in acid form

Answer 3

TTT haplotype has a significant difference

Question 4

When does ABCB1 haplotypes not have an effect

Answer 4

In other statins including fluvastatin

Question 5

Does MDR1 polys have effect on transport activities and what are they

Answer 5

No
G to T/A
C to T

Question 6

What is the main breast cancer resistance protein (ABCG2) poly and what are its effects

Answer 6

C to A - high allele frequency
Impaired protein folding and cellular processing
Reduced protein expression
Reduced transport activity
Reduced efflux
Increased drug absorption

Question 7

How is ABCG2 relavent to rosuvastatin

Answer 7

BCRP pumps rosuvastatin back into lumen
C to A variant causes lower BCRP conc
Increased rosuvastatin levels

Question 8

What is SLCO1B1 also called

Answer 8

OATP1B1

Question 9

What SLCO1B1 poly causes decreased transport

Answer 9

SLCO1B1*5

Question 10

What SLCO1B1 polys cause increased transport

Answer 10

SLCO1B114
SLCO1B120

Question 11

What causes Glucose-6-phosphate dehydrogenase (G6PDH) deficiency

Answer 11

Genetics

Question 12

Where is the G6PDH poly and what are its effects

Answer 12

exon 14 on X chromosome
so more common in males
May trigger haemolytic anaemia upon exposure to xenobiotics (e.g. Sulphamethoxazole)