Relation between AT1R Gene Polymorphism and Long-Term Outcome in Patients with Heart Failure

Abstract

Objectives: Angiotensin II plays a key role in the pathophysiology of heart failure (HF). This study examined the angiotensin II type 1 receptor (AT1R) polymorphism in patients with systolic HF and its relation to clinical manifestations and patient outcome. Methods: We genotyped 134 patients with HF and reduced systolic function for the AT1R A1166C genotype using polymerase chain reaction and restriction fragment length polymorphism. We analyzed the relationship between the AT1R A1166C polymorphism and clinical, electrocardiographic, echocardiographic and laboratory parameters in patients with ischemic and non-ischemic etiology and examined the relation between the AT1R genotype and long-term (30 months) patient survival. Results: In HF patients, frequency of the AT1R 1166C allele and specifically the CC genotype was similar to the general population, but associated with an ischemic and not a non-ischemic etiology (p = 0.02). The CC genotype was associated with more advanced disease and more severe abnormalities of renal function (p = 0.008). Survival analysis showed that AT1R CC homozygous patients had significantly higher mortality (p = 0.008; adjusted odds ratio for mortality 6.35, 95% confidence interval 1.49–11.21, p = 0.01). Conclusion: The CC AT1R genotype was associated with poor prognostic markers and increased mortality. The findings support the principle of genome-based therapies in the future treatment of HF patients.

Genetic polymorphisms associated with heart failure: A literature review

“…Polymorphism AT1R 1166C has been studied in relation to diastolic HF, 13 coronary artery disease 17 and incidence of HF. 10 , 18 Wu, et al . 13 reported that AT1R 1166C carriers were associated with a higher risk of diastolic HF, and Mishra, et al .…”

“…In contrast, two further studies failed to find any significant relationship between A1166C polymorphisms and incidence of HF. 10 , 18 …”

Association of AGTR1 gene A1166C polymorphism with the risk of heart failure: a meta-analysis

“…Based on the inclusion criteria, only 5 case-control studies (Gubaev et al, 2006;Amir et al, 2009;Zakrzewski-Jakubiak et al, 2008;Wu et al, 2008;Cameron et al, 2006) with full-text were included in this metaanalysis and 28 studies were excluded. The flow chart of study selection is summarized in Figure 1.…”

“…The published year of the studies included ranged from 2006 to 2014. The study characteristics are presented in Table 1, and contain the population studies of 4 Caucasians (Gubaev et al, 2006;Zakrzewski-Jakubiak et al, 2008;Cameron et al, 2006) and 2 Asians (Amir et al, 2009;Cameron et al, 2006). The source of the controls was based on healthy populations.…”

Cardiovascular Disease, Single Nucleotide Polymorphisms; and the Renin Angiotensin System: Is There a MicroRNA Connection?

“…In particular, a SNP has been described in which there is an A/C transversion at position +1166 (i.e., 1166 base-pairs downstream from the start codon, dsSNP# rs5186) located in the 3′-UTR of the hAT 1 R gene. The increased frequency of the +1166 C-allele has been associated with hypertension [108–115], cardiac hypertrophy [116–118], aortic stiffness [119–121], myocardial infarction [122], heart failure [123–125], abdominal aortic aneurysms [126, 127], and increased oxidative stress levels in human heart failure [128]. However, the physiological relevance of this polymorphism is uncertain because of its location within the noncoding region of the hAT 1 R gene.…”