Table 2.

Genetic variants influencing cardiovascular drug therapy: examples

Gene	Drug	Clinical effects
Drug metabolism
CYP2C9	Losartan	Decreased bioactivation and effects (PMs)45
	Warfarin	Decreased dose requirements; possible increased bleeding risk (PMs)14,46
CYP2C19	Clopidogrel	Decreased bioactivation and effect in PMs16–18
CYP2D6	metoprolol carvedilol timolol propafenone	Increased beta-blockade in PMs19,47,48
CYP3A5	atorvastatin simvastatin lovastatin	Increased lipid lowering efficacy49 increased severity of myotoxicity50
NAT2	hydralazine, procainamide	Increased risk of toxicity in PMs51
Drug transport
SLCO1B1	simvastatin	Variant non-synonymous single nucleotide polymorphism alters efficacy and increases myopathy risk15,28,52
ABCG2	many statins	Altered pharmacokinetics52
Drug targets
HMG-CoA reductase	pravastatin	Haplotype-dependent LDL lowering26
VKORC1	warfarin	Decreased dose requirements with variant promoter haplotype24
ADRB1, ADRB2	many beta- blockers	Altered vascular and heart rate effects53–55
ACE	ACE inhibitors	No effect on drug response34
Other genes
ACE	Beta-blockers in heart failure Antiarrhythmics in atrial fibrillation	Decreased response in subjects with DD genotype22,23
G-protein β3 subunit, kininogen, other loci	Thiazide diuretics	Greater reduction in diastolic and systolic blood pressure56–58

As discussed in the text, there is variability in the size of the genetic effects and in the extent to which these findings have been replicated.

Further data at the Pharmacogenetics Research Network/Knowledge base: http://www.pharmgkb.org