Genetic variation in the renin–angiotensin–aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease
Whalley, Gillian; Ellis, Katrina L.; Palmer, Barry R.; Frampton, Chris M.; Troughton, R. W.; Doughty, Robert N.; Ellis, Chris J.; Pilbrow, Anna P.; Skelton, Lorraine; Yandle, Tim G.; Richards, A. Mark; Cameron, Vicky A.
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Citation:Ellis, K. L., Palmer, B. R., Frampton, C. M., Troughton, R. W., Doughty, R. N., Whalley, G. A., ... & Cameron, V. A. (2012). Genetic variation in the renin–angiotensin–aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease. Journal of Human Hypertension.
Permanent link to Research Bank record:http://hdl.handle.net/10652/2120
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.