Pharmacogenomics (PGx)
What is Pharmacogenomics (PGx)?
Pharmacogenomics (PGx) is the science of how a person’s genetic make-up influences the way we respond (either positively or negatively) to drugs.We all know examples where some people treated with medication either respond well, while others do not respond at all, while others experience some serious adverse reaction to the medication.The current paradigm for treating patients with medication is “one size fits all” or as in some cases, medication is based on ’trial and error’.
Variable inter-individual responses to certain drugs can be influenced by a number of factors, eg age, sex, pathology, life style or co-medication.However, it is becoming more evident that genetics plays a central role.In some instances genetics accounts for up to 60% of the patient variation in responses to drugs.
Pharmacogenomics identifies individuals who are at high risk of experiencing adverse drug reactions or those who may not respond to certain medications.
Pharmacogenomics is the first step toward ’personalised medication’.
What is PGx Testing?
PGx DNA tests look for changes in genes that play a major role in either:
1. Drug Clearance
Depending upon ethnicity, between 10-25% of the population are genetically known as “poor metabolisers”, that is they do not have the enzymes within their livers to clear specific drugs from their bodies.As such, they are at increased risk of adverse drug reaction when blood concentrations of drugs increase to toxic level.These individuals require either alternate medication or much lower doses of the drug.
On the other hand, between 5-25% of the population are genetically known as “ultra metabolisers”, that is they have multiple copies of genes that code for drug clearing enzymes.Here, these individuals clear the drug so fast that they usually have no effect, therefore require much higher doses than normal.
2. Drug Transport & Action
Other genes code for either the drug transporter or drug receptor.Here individuals with genetic variants may not be able to respond to medication since the level of receptor has changed or it is no longer functioning.
Why Is PGx Important Today?
Adverse Drug Reactions (ADR):
USA
- 2.2 million adverse drug reactions per year.
- 4th – 6th leading cause of death.
- Cost of drug related morbidity and mortality $170 billion.
- ADR’s account for 5% of all hospital admissions.
- Overall incidence of serious ADR’s is 7%.
UK
- 250,000 people per year admitted to hospital with an ADR.
- 6.5% of new hospital admissions
- Estimated healthcare burden of ADRs, over £450 million.
Australia
- 140,000 ADR’s reported each year.
- One in ten GP consultations are patients who have suffered anADR.
Who Benefits From PGx?
Clinicians
- Able to make more informed decisions about drug selection and dosing, thereby improving patient safety.
- Able to identify the cause in many instances, of adverse drug reactions.
Patients
- Identifying “at-risk” individuals, will improve patient safety and reduce the frequency and severity of adverse drug reactions.
What PGx Tests are Performed Today?
| Test | Drug |
| CYP2D6 |
|
| CYP2C19 |
|
| CYP2C9 |
|
| VKORC1 |
|
| UGT1A1 |
|
What Tests Are Coming?
Test are being developed for a range or drugs, including asthma medication, statins, antidepressants, anti-Alzheimer medication and antihyperglycaemics. The tests are for the following genes:
- B2AR
- TPMT
- CETP
- APOE
- serotonin transporters
- CYP3A4
- CYP3A5
- MDR1