Genetic variation in the renin–angiotensin–aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease

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 (n¼1186) 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 (P¼0.006), and the AGT rs2478545 minor allele was associated with lower circulating natriuretic peptides (P¼0.0001–P¼0.001) and E/E1 (P¼0.018). Minor alleles of AGT SNPs rs1926723 and rs11122576 were associated with more frequent history of renal disease (Pp0.04) and type-2 diabetes (Pp0.02), higher body mass index (Pp0.02) and greater mortality (Pp0.007). AGT rs11568054 minor allele carriers had more frequent history of renal disease (P¼0.04) and higher plasma creatinine (P¼0.033). AGT rs6687360 minor allele carriers exhibited worse survival (P¼0.02). ACE rs4267385 was associated with older clinical coronary disease onset (P¼0.008) and hypertension (P¼0.013) onset, increased plasma creatinine (P¼0.01), yet greater mortality (P¼0.044). Less history of hypertension was observed with the AGTR1 rs12685977 minor allele (P¼0.039). Genetic variation within the RAAS was associated with cardiovascular risk factors and accordingly poorer survival.