Table 1. Pharmacogenetics of Cardiovascular Disease.

Disease	Gene	Polymorphism	Function	Therapeutic Implications
Heart Failure
RAAS	ACE	D/I	ACE D: higher ACE activity and A II levels	ACE inhibitors
				Beta-blockers
	Aldosterone synthase	Promoter -344 T/C	-344 C: increased transcriptional activity and aldosterone production	ACE inhibitors
				Aldosterone receptor antagonists
β-adrenergic receptors	β1-adrenergic receptors	Arg389Gly	Arg: increased adrenergic signal	Beta-blockers
				ACE inhibitors
	β2-adrenergic receptors	Gly49Ser	Gly: enhanced down regulation	Beta-blockers
		Gly16Arg	Receptor down regulation	Beta-blockers
		Gln27Gly
α-adrenergic signaling	α-2C receptor	α-2C Deletion	Deletion: decreased uptake of norepinephrine	Beta-blockers
	G protein β3 subunit	C825T	C825T: increased α-adrenergic signaling, lower plasma renin	ACE inhibitors
Nitric oxide	NOS3	Asp298Glu	Asp: associated with lower NOS3 activity	ACE inhibitors
Endothelin system	EDN1	IVS-4 G/A Lys198Asn	Unknown	Beta-blockers
Arrhythmia
QT interval	SCN5A, KCNH2, KCNQ1, KCNJ2, KCNE1 NOS1AP		Ion channel function	QT-prolonging antiarrhythmic drugs, antibiotics, antipsychotics
			NO synthase pathway	QT prolonging agents
Anticoagulant therapy
Cytochrome P450	CYP2C9	*2 and *3	Clearance of warfarin, risk of bleeding	Warfarin
Vitamin K oxidase	VKORC1	1173C/T	Reduced metabolism of vit. K, higher warfarin dose requirement	Warfarin
Antiplatelet Agents
Cytochrome P450	CYP2C19	*2	Decreased conversion of active metabolite, loss-of-function	Clopidogrel

Legend: ACE, angiotensin-converting enzyme; RAAS: renin angiotensin aldosterone system; NOS3, Endothelial nitric oxide synthase; EDN1, endothelin 1; A II, angiotensin II; D, deletion; I, insertion. From McNamara et al. (16), Roden et al. (2, Mestroni et al. (9).