Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure

AIMS Racial differences in survival outcomes point towards a genetic role in the pathophysiology of heart failure. Furthermore, contemporary evidence links genetics to heart failure (HF) predisposition. We tested for a difference in prevalence of 10 renin-angiotensin-aldosterone system (RAAS)-related gene polymorphisms between a homogenous population of HF patients and healthy controls. METHODS One hundred and eleven healthy volunteers and 58 HF patients were included in this study. The healthy control group consisted of males aged between 18 and 35 years old. The HF group consisted of patients (89.7% male) who were 63.8 +/- 7.9 years old, were in New York Heart Association (NYHA) class II-III and had a documented left ventricular ejection fraction (LVEF) <= 40% within the previous 6 months. Despite being treated maximally for their condition with angiotensin-converting-enzyme (ACE)-inhibitors and beta-adrenoceptor blockers, they continued to be symptomatic and, as such, were a highly specialized and homogeneous patient population. Both groups were composed of Canadian Caucasians. The analyzed polymorphisms were: ACE (I/D), angiotensin-II-receptor-type-1 (AGTR1)(A1166C), angiotensinogen (AGT)(M235T and T174M), endothelial-nitric-oxide-synthase (eNOS)(T-786C and Glu298Asp), adrenergic-receptor-a2 (ADRB2)(Gln27Glu), bradykinin-receptor-beta 2 (BDKRB2)(+9/-9), aldosterone-synthase (CYP11B2)(T-344C) and adducin-1 (ADD1)(Gly460Trp). RESULTS The AGT (T235) allele (P = 0.0025, OR 2.02, 95% CI 1.24, 3.30) was found to be more prevalent in our HF group. The AGT (174M)-AGT (235T) haplotype was also associated with the HF phenotype (P = 0.0069). Exploratory evaluation of gene-gene combinations revealed an indicative association of the AGT (T235)/ACE(D) combined polymorphisms in the HF group (P = 0.02, OR 2.12, 95% CI 1.11, 4.06). CONCLUSIONS This study demonstrates that the SNPs of AGT may be associated with HF in our population and that the AGT/ACE gene combination may play an important role in disease predisposition.