Pharmacogenomics: Learning exercise 2

Last updated: Tuesday, March 12, 2024

This is Holly. She is 34 years old and a routine blood test at her GP surgery has identified a total cholesterol of 13.2 mmol/L and an LDL of 7.1 mmol/L.

Her liver and renal function are normal. Her height is 1.64 metres and her weight is 63 kg. She has no other significant medical history and she is not taking any other medication.

Her father had a myocardial infarction at 54 years of age and physical examination shows tendon xanthomata.





➔ What signs, symptoms or other information might suggest familial hypercholesterolemia (FH) in this case? What information sources might you use to help you?
Potential information resources include the NICE Clinical Knowledge Summary on familial hypercholesterolaemia.

The Genomic Education Programme has information in the GeNotes Knowledge Hub and in the In the Clinic section. 
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Holly consents to genetic screening for FH and she is found to be heterozygous for a pathogenic variant in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) (if you need a refresher on these terms, go back to the Genomics and the NHS page).
➔ What input could a pharmacist or pharmacy technician have at this stage?
Management of FH is usually a combination of healthy lifestyle and lipid lowering therapy. Pharmacists and pharmacy technicians can help with advice on modifiable cardiovascular risk factors such as smoking, high blood pressure, obesity and alcohol. 
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➔ Holly has a 10-year-old son. Does his mother’s diagnosis have any impact upon them?
Yes. FH is an inheritable autosomal dominant disease so there is a chance that he will have inherited the condition from his mother. Close family members (parents, brothers, sisters, children) of someone with a genetically confirmed diagnosis of FH should be identified and offered testing. This can identify people with the condition early and allow effective treatment to be started reducing the risk of long-term morbidity or mortality. 


Following her diagnosis Holly has been referred to a specialist and has been started on a high-intensity statin, atorvastatin 80mg  once daily. 

A couple of months later she contacts the GP surgery to say she has had a direct-to-consumer (DTC) pharmacogenomic test done privately and would like to talk to someone about the results.

An appointment is set up with the practice pharmacy team. Holly brings in the results of the DTC test that she ordered over the internet. This includes the following information; 

  • CYP2C19 *1/*35 Intermediate metaboliser 
  • CYP2C9 *1/*9 Normal metaboliser 
  • CYP2D6 *2/*41 Normal metaboliser 
  • CYP3A4 *1/*1 Normal metaboliser 
  • SLCO1B1 Decreased function 
  • DPYD *1/*1 Normal metaboliser 
  • TPMT/NUDT15 Normal metaboliser 
She is not currently experiencing any adverse effects from her newly-started statin, and is otherwise fit and well.
➔ As a pharmacist or pharmacy technician how would you interpret these results? Is there anything that might be of concern or should be investigated further?
The analytical validity, sensitivity, and utility of private DTC pharmacogenomic tests are not subject to the same regulation or standards as NHS laboratories. Therefore, healthcare professionals should be cautious when interpreting them or if being asked to use them to influence treatment choice. Clinical and family history should still be used in assessment.

It also may not be clear how many variants were tested for each CYP or enzyme. The fewer variants looked at, the higher the risk of a false negative result.

In this instance the SLCO1B1 result may be concerning for someone on a high-intensity statin.

The SmPC for atorvastatin mentions that in patients with SLCO1B1 polymorphism there is a risk of increased exposure of atorvastatin, which may lead to an increased risk of rhabdomyolysis. Decreased function of SLCO1B1 may mean a higher risk of statin-induced myopathy so they should be monitored and treatment managed as clinically appropriate.