Abstract
This study examined renin-angiotensin-aldosterone (RAAS) system gene variants for associations with cardiovascular risk factors and outcomes in coronary heart disease. Coronary disease patients (n = 1186) were genotyped for 21 single-nucleotide polymorphisms (SNPs) within angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-II type-1 receptor (AGTR1) and aldosterone synthase (CYP11B2). Associations with all-cause mortality and cardiovascular readmissions were assessed over a median of 3.0 years. The AGT M235T 'T' allele was associated with a younger age of clinical coronary disease onset (P = 0.006), and the AGT rs2478545 minor allele was associated with lower circulating natriuretic peptides (P = 0.0001-P = 0.001) and E/E-1 (P = 0.018). Minor alleles of AGT SNPs rs1926723 and rs11122576 were associated with more frequent history of renal disease (P <= 0.04) and type-2 diabetes (P <= 0.02), higher body mass index (P <= 0.02) and greater mortality (P <= 0.007). AGT rs11568054 minor allele carriers had more frequent history of renal disease (P = 0.04) and higher plasma creatinine (P = 0.033). AGT rs6687360 minor allele carriers exhibited worse survival (P = 0.02). ACE rs4267385 was associated with older clinical coronary disease onset (P = 0.008) and hypertension (P = 0.013) onset, increased plasma creatinine (P = 0.01), yet greater mortality (P = 0.044). Less history of hypertension was observed with the AGTR1 rs12685977 minor allele (P = 0.039). Genetic variation within the RAAS was associated with cardiovascular risk factors and accordingly poorer survival.