Background and Objectives: Pharmacogenetics has the potential to maximize drug efficacy and minimize adverse effects of cardiovascular disease (CVD) but its translation into clinical practice been slow. However, recent advancements in genotyping and statistical methodologies have now provided robust evidence in the support of personalized medicine. This thesis addresses how the advancements in pharmacogenetics may help to gain novel insights into existing drug targets, inform and guide clinical decision-making and validate potential disease target pathways.
Methods: This was achieved by exploring whether the COX-2 genetic variant (rs20417) is associated with a decreased risk of CVD outcomes, assessing whether bile acid sequestrants (BAS) are associated with a reduced the risk of coronary artery disease (CAD) using the principles of Mendelian Randomization and investigating whether genetic variants associated with dysglycaemia are associated with an increased risk of CAD.
Results: We demonstrated that COX-2 carrier status was associated with a decreased risk of major cardiovascular outcomes. Furthermore, we also showed that BAS appear to be associated with a reduced risk of CAD and genetic variants associated with HbA1c and diabetes were associated with an increased risk of CAD.
Conclusions: The convergence of technological and statistical advancements in pharmacogenetics have led to a more high-quality and cost-effective means of assessing the effect of CVD therapeutic agents. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/16885 |
| Date | 06 1900 |
| Creators | Ross, Stephanie |
| Contributors | Pare, Guillaume, Clinical Epidemiology/Clinical Epidemiology & Biostatistics |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | Thesis |
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