Genes and Drugs
Summer of Research project by Kate Kilpatrick, University of Auckland, supervised by Dr Patrick Gladding.
Huge advances have been made in cardiovascular medicine in recent decades, but the application of some of these advances in real world practice has been minimal. Kate Kilpatrick and her supervisor noted that antiplatelet therapy in acute coronary syndrome (ACS) was an area where advances in targeting therapies hadn’t yet been studied in New Zealand. In her summer of research project, Kate aimed to discover the benefits of personalised medicine (e.g. using data from non-traditional sources such as genome mapping) in ACS in comparison to current practice.
The basis for Kate’s work is that:
- There are three main antiplatelet drugs: clopidogrel, prasugrel and ticagrelor.
- Studies have already shown that ticagrelor has better results in patients who don’t respond to clopidogrel due to genetic variants in the CYP2C19 gene .
- Studies have also shown that clopidogrel is associated with adverse effects in patients that also have the CYP2C19*2 variant [2,3].
- The CYP2C19*2 genetic variant occurs in 13% of Caucasians, 18% of African Americans and 29% of East Asians.
- CYP2C19*2 also occurs in 24% of Māori, in comparison to 15% of NZ Europeans .
- The rarer CYP2C19*3 variant makes clopidogrel even less effective, and occurs in 1.8% of Pacific peoples and Māori [4,5].
A conclusion from these facts is that patients who carry the CYP2C19*2 genetic variant (genotype) should avoid clopidogrel. Kate’s research goal was to measure the health outcomes of patients genotyped for CYP2C19, and thereby who received personalised healthcare, in contrast to those who received generic treatment. The research is still ongoing but the majority of data has been collected, including patient information, genotyping status, outcomes, and inpatient medication data.
Once complete, the results of this project will aid in the development of an algorithm with the intention of helping clinicians with their decision making process around management of ACS. Kate hopes to incorporate this algorithm into e-prescribing platforms that clinicians use to prescribe medication to patients. Being able to predict what types of medicine will be most effective in treating certain health issues will improve the outcome for all patients, reduce the number of visits, and improve the efficiency of the system overall.
This particular project has the potential to benefit Māori and Pacific people especially, due to their higher chances of having the genotypes mentioned earlier. Kate’s research will support existing studies showing that patient-specific, precise treatment is more effective than generic diagnosis. Research like this can also result in cost savings for the healthcare industry. Clinicians will become more precise and therefore less likely to make mistakes that can lead to adverse outcomes for patients or resources being wasted. Precision medicine is for everyone’s benefit.
Kate Kilpatrick is among a group of students who took part in the summer of research programme funded by Precision Driven Health. This month we are featuring a blog series examining these projects. While at an elementary stage and considered to be a ‘proof of concept’, these projects offer fresh insights into what the world of healthcare will look like when precision medicine is fully implemented.
1. Wallentin, L., et al., Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. The Lancet. 376(9749): p. 1320-1328.
2. Mega, J., et al. Cytochrome P450 Genetic Variants Predict Cardiovascular Outcomes following Treatment with Clopidogrel but not with Prasugrel. in American Heart Association. 2008. New Orleans.
3. Mega, J.L., et al., Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation, 2009. 119(19): p. 2553-60.
4. Lea, R.A., et al., Allele frequency differences of cytochrome P450 polymorphisms in a sample of New Zealand Maori. N Z Med J, 2008. 121(1272): p. 33-7.
5. Hsu, H., et al., A high incidence of polymorphic CYP2C19 variants in archival blood samples from Papua New Guinea, in Human Genomics (In Press). 2008.
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