RAAS and adrenergic genes in heart failure: Function, predisposition and survival implications

Table 3 Effect of adrenergic gene polymorphisms on survival of patients with heart failure

Ref.	Sample, design1	Endpoints	Follow-up (mo)	Mortality rate (%)	SNP	Main findings
β adrenergic receptor type 1
[15]	10402	AD, HZ	48	19	Arg389Gly	Increased survival in Arg389 homozygous treated with bucindolol
[58]	1843	AD, HT	24-60	38	Ser49Gly	Decreased survival in Ser49Ser patients
[76]	6002	AD, HZ	7-17	26	Arg389Gly	No association with endpoints
[50]	2013	AD, CD	18-62	28	Arg389Gly, Ser49Gly	Increased survival in Arg389 allele carriers on high dose beta-blockers
[77]	4443	CD, HT	41 (median)	25	Arg389Gly, Ser49Gly	No association with endpoints
[78]	2273	AD, HT	48	18	Arg389Gly, Ser49Gly	No association with endpoints
[79]	6373	AD, HT	35 (mean)	23	Arg389Gly, Ser49Gly	No association with endpoints
β adrenergic receptor type 2
[59]	2593	AD, HT	22 (mean)		Gly16Arg, Gln27Glu, Thr164Ile	Increased risk of death in Thr164Ile patients
[77]	4443	CD, HT	41 (median)	25	Gly16Arg, Thr164Ile	No association with endpoints
[78]	2273	AD, HT	48	18	Gly16Arg, Gln27Glu	Increased risk of death (haplotype)
[80]	313	AD, HT	24	3	Thr164Ile	Worsening HF in Thr164Ile patients
[81]	4433	AD	36 (median)		Thr164Ile	Improved survival in Thr164Thr patients treated with beta-blockers
α adrenergic receptor type 2
[78]	2273	AD, HT	48	18	Del322-325	No association with endpoints
[79]	6373	AD, HT	35 (median)	23	Del322-325	No association with endpoints
[82]	3453	AD, HT	60 (mean)	18	Del322-325	Reduced risk of death and end-points
G-protein kinase receptor 5
[35]	3752	AD, HT	30 (mean)		Gln41Leu	Increased survival in Leu41 African-American patients treated with beta-blockers. No impact on Caucasians

¹Study design;

²Placebo controlled randomized trial;

³Non-randomized, single group assignment. SNP: Single nucleotide polymorphism; AD: All cause mortality; CD: Cardiac mortality; HT: Heart transplantation; HZ: Hospitalizations.