Epistatic effects between two genes in the renin-angiotensin system and systolic blood pressure and coronary artery calcification.
Sharon L.R. Kardia, Lawrence F. Bielak, Leslie A. Lange, James M. Cheverud, Eric Boerwinkle, Stephen T. Turner, Patrick F. Sheedy II, Patricia A. Peyser
Med Sci Monit 2006; 12(4): CR150-158
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