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. 2013 Apr;27(4):237-44. doi: 10.1038/jhh.2012.24. Epub 2012 Jun 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Angiotensinogen / genetics
  • Comorbidity
  • Coronary Artery Disease / ethnology
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / mortality*
  • Cytochrome P-450 CYP11B2 / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / genetics
  • Hypertension / mortality
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Middle Aged
  • New Zealand / epidemiology
  • Odds Ratio
  • Peptidyl-Dipeptidase A / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Proportional Hazards Models
  • Receptor, Angiotensin, Type 1 / genetics
  • Renin-Angiotensin System / genetics*
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • AGT protein, human
  • AGTR1 protein, human
  • Receptor, Angiotensin, Type 1
  • Angiotensinogen
  • Cytochrome P-450 CYP11B2
  • ACE protein, human
  • Peptidyl-Dipeptidase A