Background: Coronary artery calcification (CAC) is an important indicatorof future coronary artery disease events. Since elevated blood pressure (BP) is an important predictorof CAC, genetic polymorphisms in the renin-angiotensin system and their interaction may play a role inexplaining CAC quantity variation. Material/Methods: As part of the Epidemiology of Coronary Artery CalcificationStudy, 166 asymptomatic women and 166 asymptomatic men were genotyped for the insertion/deletion polymorphismin 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-wayanalysis of variance (ANOVA) method. Results: Based on a two-way ANOVA model, there was no evidence forepistasis for either systolic BP or CAC in either men or women. However, using a novel method, we foundevidence of significant gene-gene interaction in systolic BP in men and gene-gene interaction in bothsystolic BP levels and CAC quantity in women. Conclusions: Our study demonstrates that new methods ofassessing epistasis maybe important in understanding the complex genetics of systolic blood pressureas well as subclinical coronary atherosclerosis.

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