title: 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 (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.
authors: Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago-Christchurch, Christchurch, New Zealand. katrina.ellis@otago.ac.nz
authors: K L
authors: KL
authors: Ellis
authors: B R
authors: BR
authors: Palmer
authors: C M
authors: CM
authors: Frampton
authors: R W
authors: RW
authors: Troughton
authors: R N
authors: RN
authors: Doughty
authors: G A
authors: GA
authors: Whalley
authors: C J
authors: CJ
authors: Ellis
authors: A P
authors: AP
authors: Pilbrow
authors: L
authors: L
authors: Skelton
authors: T G
authors: TG
authors: Yandle
authors: A M
authors: AM
authors: Richards
authors: V A
authors: VA
authors: Cameron
mesh_terms: D017668:Age of Onset; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics* / Q000401:mortality*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000401:mortality; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009520:New Zealand / Q000453:epidemiology; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: C534931:AGT protein, human; C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D019405:Cytochrome P-450 CYP11B2; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A