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


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.
Department of Epidemiology, University of Michigan, Ann Arbor, MI 48104-3028, USA. skardia@umich.edu
Sharon L R
SL
Kardia
Lawrence F
LF
Bielak
Leslie A
LA
Lange
James M
JM
Cheverud
Eric
E
Boerwinkle
Stephen T
ST
Turner
Patrick F
PF
Sheedy
Patricia A
PA
Peyser
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics; D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics*; D002114:Calcinosis / Q000235:genetics*; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics; D003331:Coronary Vessels / Q000473:pathology*; D004247:DNA / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics*
D000808:Angiotensinogen; D004247:DNA; D007703:Peptidyl-Dipeptidase A