1639βG > A () and 3730βG > A genotypes () in VKORC1, the 8016βG > A genotype in GGCX (), and the 42613βA > C genotype in CYP2C9 () were associated with effective warfarin dose
Antiplatelets
Meta-analysis of 9 different studies (CLARITY TIMI 28, EXCLESIOR, TRITION TIMI 38, AFIJI, FASSTS-MI, RECLOSE, ISAR, CLEAR PLATELETS, Intermountain) [35]
Composite outcome (cardiovascular death/MI/stroke) and stent thrombosis
CYP2C19/1 or 2 reduced function alleles (*2, *3, *4, *5, *6, *7, and *8)
9685 patients (91% had PCI, 54% had ACS)/clopidogrel
Carriers of 1 (HR 1.55; 95% CI, 1.11β2.17) or 2 (HR 1.76; 95% CI, 1.24β2.50) reduced-function CYP2C19 alleles had higher risk of composite outcome events
CYP2C19/1 or 2 reduced function alleles (*2, *3, *4, *5, *6, *7, and *8) ABCB1/3435C β T
2932 patients with ACS undergoing PCI/clopidogrel versus prasugrel
TT homozygotes of ABCB1 genotype had increased risk of the composite outcome compared to CT or CC carriers (HR 1.72, 95% CI 1.22β2.44). Carriers of a CYP2C19 reduced-function allele only (Kaplan-Meier event rate 11.5%), ABCB1 3435 TT homozygotes only (Kaplan-Meier event rate 12.6%), or both (Kaplan-Meier event rate 13.6%) had increased risk of composite outcome (pooled HR 1.97, 95% CI 1.38β2.82). No significant genotype-prasugrel interaction was reported
CYP2C19/1 or 2 reduced function alleles ABCB1/3435C β T
10285 patients with ACS undergoing non-CABG/clopidogrel versus ticagrelor
Either with (HR 0.77, 95% CI 0.60β0.99) and without (0.86, 0.74β1.01, ) any CYP2C19 reduced-function alleles patients on ticagrelor experienced lower risk of composite outcome compared to patients on clopidogrel (interaction ). Independently of ABCB1 genotype, patients on ticagrelor had lower risk of the composite outcome compared to clopidogrel users (interaction ; HR 0.71, 95% CI 0.55β0.92). No significant interaction was found on treatment and genotype regarding major bleeding
429 white healthy Amish individuals/clopidogrel; results replicated in 227 undergoing PCI
13 SNPs in 10q24 region, where CYP2C18βCYP2C19βCYP2C9βCYP2C8 gene cluster is found, were associated with reduced response to clopidogrel. allele carriers were at higher risk for composite outcome (adjusted HR 2.42 95% CI 1.18β4.99)
COX-1/C116T, del 137β142, C144T, G6841A, G7331C, A7742A, C10427A, C10608A, del 10675A, G12254A, T12378C, G19187A, C19242T, G19255A
68 with recurrent stroke/ASA
14 variants of the Cox-1 gene were identified and 7 involved amino acid substitutions of the Cox-1 molecule. None of the mutations were located near the catalytic site
ABCB1: ATP-binding cassette subfamily B, ACEI: angiotensin convertin enzyme inhibitors, ACE I/D: angiotensin convertin enzyme insertion/deletion, ACS: acute coronary syndrome, ADD1: Ξ±-adducin, ADRB: Ξ²-adrenergic receptor, AGT: angiotensinogen, AGTR1: angiotensin receptor II type 1, APO E: apolipoprotein E, BP: blood pressure, CABG: coronary artery bypass graft, CAD: coronary heart disease, CD: cluster of differentiation, CEPT: cholesteryl ester transfer protein, CHD: coronary artery disease, COX: cyclooxygenase, CVD: cerebrovascular disease, CYP: cytochrome P, FGB: fibrinogen beta, GRK: G-protein-coupled receptor kinase, GWA: genome-wide association, HMG-CoR: hydroxyl-methylcoenzyme A reductase, HR: hazard ratio, HTN: hypertension, KCNMB: conductance calcium and voltage-dependent potassium channel, KIN 6: kinesin family member 6, LDLR: low-density lipoprotein receptor, LIPC: human hepatic lipase, MGP: matrix Gla protein, MI: myocardial infarction, MMP: matrix metalloproteinase, NIHSS: National Institute of Health stroke scale, NOS: nitric oxide synthase, NPPA: atrial natriuetic polypeptide precursor, OR: odds ratio, PAI: plasminogen activator inhibitor, PCI: percutaneous coronary intervention, SI: sinergy index, TAFI: thrombin-activable fibrinolysis inhibitor, verapamil SR: verapamil-sustained release, VKORC1: vitamin K epoxide reductase complex subunit 1.
