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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 volume 27, pages 237–244 (2013)Cite this article

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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/E1 (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.

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Acknowledgements

We thank the study participants, the clinical research staff of the Cardioendocrine Research Group (Christchurch) and the Cardiovascular Research Laboratory (Auckland) and are grateful to the assay staff of Cardioendolab, University of Otago, Christchurch. This work was funded by the Health Research Council of New Zealand (Auckland, New Zealand); New Zealand Lotteries Grant Board (Wellington, New Zealand), and National Heart Foundation of New Zealand (Auckland, New Zealand).

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  1. Department of Medicine, Christchurch Cardioendocrine Research Group, University of Otago-Christchurch, Christchurch, New Zealand

    K L Ellis, B R Palmer, C M Frampton, R W Troughton, A P Pilbrow, L Skelton, T G Yandle, A M Richards & V A Cameron

  2. Department of Medicine, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand

    R N Doughty, G A Whalley & C J Ellis

  3. Department of Medical Imaging, Unitec Institute of Technology, Auckland, New Zealand

    G A Whalley

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  1. K L Ellis
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Correspondence to K L Ellis.

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Ellis, K., Palmer, B., Frampton, C. et al. Genetic variation in the renin–angiotensin–aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease. J Hum Hypertens 27, 237–244 (2013). https://doi.org/10.1038/jhh.2012.24

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