Drugs and the Genome

Question 1

What mode of inheritance is present in family hypercholesterolaemia?

Answer 1

Autosomal dominant - mutation in LDL receptor

Question 2

What is the presentation of family hypercholesterolaemia?

Answer 2

Corneal arcus, xanthelasma

Question 3

What is the treatment of familial hypercholesterolaemia?

Answer 3

PCSK9 inhibitors e.g. evolocumab, alirocumab, bococizumab

Question 4

Describe the aetiology of cystic fibrosis

Answer 4

1 in 25 are carriers (mutation in CFTR gene), white Europeans generally

Question 5

Describe the treatment of cystic fibrosis

Answer 5

combination of ivacaftor and lumacaftor (improves lung function, prevents channel degradation and improves channel function) in those 12 and above with the F508 mutation

Question 6

What is a thiopurine methyl transferase (TPMT) test?

Answer 6

Tests for the enzyme which metabolises azathioprine and 6-mercaptopurine to predict whether someone will experience severe haematopoietic toxicity

Question 7

What genetic mutations may alter the effects of warfarin?

Answer 7

• Those with group A VKORC1 polymorphisms achieve a therapeutic INR more rapidly, so may be at risk of bleeding
• CYP2C9 polymorphisms don’t influence the time to effective INR but they do shorten the time the INR is >4