Epistatic effects between two genes in the renin-angiotensin system and systolic blood pressure and coronary artery calcification
A new paper by Dr. Sharon Kardia et al. in Medical Science Monitor reports evidence for epistatic effects of the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene and the -6 promoter polymorphism of the angiotensinogen (AGT) gene on systolic blood pressure and coronary artery calcification. It is important to note that this is one of the few examples of the successful application of Dr. Jim Cheverud's physiological epistasis approach in a human study. Cheverud's original paper on physiological epistasis appeared in Genetics in 1995 [see PubMed].
Here is Dr. Kardia's paper:
Kardia SL, Bielak LF, Lange LA, Cheverud JM, Boerwinkle E, Turner ST, Sheedy Ii PF, Peyser PA. Epistatic effects between two genes in the renin-angiotensin system and systolic blood pressure and coronary artery calcification. Med Sci Monit. 2006 Mar 28;12(4):CR150-158 [PubMed]
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.