Epistatic effects between two genes in the renin-angiotensin system and systolic blood pressure and coronary artery calcification

Med Sci Monit. 2006 Apr;12(4):CR150-8. Epub 2006 Mar 28.


Background: Coronary artery calcification (CAC) is an important indicator of future coronary artery disease events. Since elevated blood pressure (BP) is an important predictor of CAC, genetic polymorphisms in the renin-angiotensin system and their interaction may play a role in explaining CAC quantity variation.

Material/methods: As part of the Epidemiology of Coronary Artery Calcification Study, 166 asymptomatic women and 166 asymptomatic men were genotyped for the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene and the -6 promoter polymorphism of the angiotensinogen (AGT) gene. We used a novel method to detect gene-gene interaction and compared it to the standard two-way analysis of variance (ANOVA) method.

Results: Based on a two-way ANOVA model, there was no evidence for epistasis for either systolic BP or CAC in either men or women. However, using a novel method, we found evidence of significant gene-gene interaction in systolic BP in men and gene-gene interaction in both systolic BP levels and CAC quantity in women.

Conclusions: Our study demonstrates that new methods of assessing epistasis maybe important in understanding the complex genetics of systolic blood pressure as well as subclinical coronary atherosclerosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensinogen / genetics
  • Base Sequence
  • Blood Pressure / genetics*
  • Calcinosis / genetics*
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / genetics
  • Coronary Vessels / pathology*
  • DNA / genetics
  • Epistasis, Genetic*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Renin-Angiotensin System / genetics*


  • Angiotensinogen
  • DNA
  • Peptidyl-Dipeptidase A