Table 3.

A summary of the results of most interesting studies on the β-adrenergic antagonists presented in this review.

Drug	Population/Study Design	Gene	Polymorphism	Result	Ref.
Atenolol	White, Hispanic, and Black patients with hypertension and documented CAD	ADRB1	Ser49-Arg389	The presence of this haplotype was associated with a considerable risk of all-cause death among patients randomly assigned to verapamil SR (HR 8.58, 95% CI 2.06–35.8) but not atenolol (HR 2.31, 95% CI 0.82–6.55), suggesting a protective role for the β-blocker.	[59]
Atenolol	Participants of the SPS3 (Secondary Prevention of Small Subcortical Strokes) trial with hypertension	ADRB1	Ser49Gly (rs1801252)	Gly49 carriers treated with β-blockers had increased risk of adverse outcomes. Gly49 carriers treated with β-blockers had a 3-fold increased risk, while Gly49 carriers without β-blocker treatment had a 2-fold risk; thus, it seems that β-blocker treatment could amplify the effects on the Gly49 allele.	[60]
Metoprolol	White, African American, and Hispanic patients with hypertension	ADRB1	Arg389Gly (rs1801253)	Daytime diastolic BP responses to metoprolol among carriers of the Arg/Arg genotype were 3-fold greater compared to the Gly allele carriers (-13.3% +/- 8.4% versus -4.5% +/- 8.2%, p =.0018).	[61]
Carvedilol	Subjects with uncomplicated essential hypertension from the Jilin province of China	ADRB1	Arg389Gly (rs1801253)	In Chinese hypertensive 389Arg/Arg patients, treatment with carvedilol reduced BP to a greater extent (4-fold) than in individuals carrying the Gly allele (10.61 vs. 2.62 mm Hg, p = 0.013).	[62]
Metoprolol	Healthy individuals and patients with essential hypertension	ADRB1	Arg389Gly (rs1801253)	Subjects carrying the Gly/Gly genotype showed greater antihypertensive responses to metoprolol than the heterozygotes (p = 0.027).	[63]
Atenolol	Hypertensive Caucasians and African American participants from the PEAR trial	GRK4	A142V (rs1024323) R65L (rs2960306)	GRK4 65L and 142V variants, as well as the presence of the 65L-142V haplotype, significantly reduced the response to β-blocker monotherapy and also enhanced the risk of adverse long-term CV outcomes.	[66]
Atenolol	European American participants of the PEAR and PEAR-2 study	FGD5	rs294610	Carriers of the A allele had a considerably better BP response than non-carriers	[68]
Metoprolol Atenolol	African American hypertensive participants	SLC25A31	rs201279313	Heterozygotes versus the wild-type genotype had better diastolic BP responses to atenolol monotherapy, metoprolol monotherapy, and atenolol add-on therapy: −9.3 versus −4.6, −9.6 versus −4.8, and −9.7 versus −6.4 mm Hg, respectively (3-group meta-analysis p = 2.5×10(-8), β = −4.42 mm Hg per variant allele)	[73]
Atenolol	Finnish patients of the LIFE study	ACY3	rs2514036	Variation at the transcription start site of ACY3 was associated with a blood pressure response to atenolol in men	[74]

PEAR—Pharmacogenomic Evaluation of Antihypertensive Responses; CV—cardiovascular; LIFE—Losartan Intervention For Endpoint reduction in hypertension study.