Table 1. Examples of genetic variants influencing response to cardiovascular drugs.
| Gene | SNP | Chr | Position | Reported effect on function | Possible implication for clinical practice |
|---|---|---|---|---|---|
| Tier 1 – Strong level of evidence for clinical translation | |||||
| CYP2C19*2 | rs4244285 | 10 | 96531606 | Reduced enzyme function→ Resistance to clopidogrel | For carriers of 1 or 2 copies of *2 allele, consider alternate antiplatelet agent when undergoing PCI or after ACS. Consider higher maintenance dose in heterozygotes |
| VKORC1 | rs9923231 | 16 | 31107689 | Increased sensitivity to warfarin | For carriers of 1 or 2 copies of the A allele, consider a lower initial dose of warfarin compared with carriers of the G allele (use in conjunction with CYP2C9 genotype information) |
| CYP2C9*2 | rs1799853 | 10 | 96702047 | Increased sensitivity to warfarin | For carriers of 1 or 2 copies of the *2 allele, consider a lower initial dose of warfarin (use in conjunction with CYP2C9 genotype information) |
| CYP2C9*3 | rs1057910 | 10 | 96741053 | Increased sensitivity to warfarin | For carriers of 1 or 2 copies of the *3 allele, consider a lower initial dose of warfarin (use in conjunction with VKORC1 genotype information) |
| SLCO1B1 | rs4149056 | 12 | 21331549 | Increased likelihood of simvastatin-related myotoxicity | For carriers of this variant consider an alternate lipid lowering therapy |
| Tier 2 – Weaker evidence, clinical implementation premature | |||||
| ABCB1-C3435T | rs1045642 | 7 | 86976581 | Resistance to clopidogrel | If genotype known, may consider alternate antiplatelet agent |
| CYP2C19*17 | rs12248560 | 10 | 96511647 | Increased clopidogrel efficacy | Concern for bleeding with clopidogrel, monitor patients closely if genotype known |
| CYP2C19*3 | rs4986893 | 10 | 96540410 | Resistance to clopidogrel | If genotype known, may consider alternate antiplatelet agent |
| ADRB1-R389G | rs1801253 | 10 | 115805056 | Increased response to beta-blockers | May consider alternate therapeutic class (e.g. maximize ACEi over beta-blocker in heart failure or calcium channel antagonist for rate control in atrial fibrillation) |
| ADRB1-R389G | rs1801253 | 10 | 115805056 | Associated with successful rate control strategy for AF | May assist in selection of atrial fibrillation treatment strategy (i.e. rate versus rhythm control) |
| 4q25 (intergenic near PITX2) | rs10033464 | 4 | 136232206 | Associated with successful rhythm control strategy for AF | May assist in selection of atrial fibrillation treatment strategy (i.e. rate versus rhythm control) |
| KCNE1-D85N | rs1805128 | 21 | 35821680 | Increased risk of drug-induced TdP | Assist in assessment of risk for drug-related TdP |
ACEi, angiotensin converting enzyme inhibitor; AF, atrial fibrillation; SNP, single-nucleotide polymorphism; TdP, torsades de pointes