Abstract 336: Angiotensinogen Gene Polymorphism Confers a Multiple Risk Factor for Atherosclerosis and Its Susceptibility Traits
Angiotensinogen (AGT) constitutes a pivotal component of the renin-angiotensin system which controls the systemic blood pressure and several other cardiovascular functions. In order to evaluate the role of the AGT gene polymorphism in atherosclerosis (CAD) and its risk factors, we first sequenced the gene in 200 individuals in search of informative SNPs. Of the >100 SNPs identified, we proceeded to evaluate the association of 8 variants in 3232 CAD cases versus 2292 angiographed controls by the Applied Biosystems real-time PCR system. Of the studied variants, the recessive mode of inheritance (TT) of rs3789679C>T [Odds ratio(95% Confidence Interval) = 1.23(1.05-1.45); p=0.012]; TT of rs699C>T [1.21(1.11-1.32); p<0.0001] as well as the dominant models (AG+GG) of rs5051A>G [1.22(1.10-1.37; p<0.0001) and AG+GG of rs2067853A>G [1.23(1.07-140);p=0.003] conferred risk for CAD. Interestingly, rs699 (p<0.0001), rs5051 (p=0.003) and rs2067853 (p=0.001) were equally implicated in hypertension, while the rs699 was further associated with hypercholesterolaemia (p=0.002) and hypertriglyceridaemia (p<0.0001), and the rs5051 was similarly associated with type 2 diabetes mellitus (T2DM) (p=0.011). One 8-mer haplotype from the 8 studied SNPs ACGGATAT (χ2=9.83; p=0.0017) and several of its variants, including the 7-mer ACGGATA (χ2=9.40; p=0.0022), 6-mer GGATAT (χ2=11.54; p=0.0007) and 5-mer GATAT (χ2=10.89; p=0.001) conferred significant risk for CAD. Furthermore, three 8-mer haploptypes GTGGGTGG (χ2=6.96; p=0.0083), ACGGGTAT (χ2=4.70; p=0.030) and GTAGGCGG (χ2=5.69; p=0.017) were associated with HTN. Similar trends were also observed for T2DM, obesity and hyperlipidaemia. These observations show that the AGT gene polymorphism confers a common risk for atherosclerosis and its major susceptibility traits.
- © 2012 by American Heart Association, Inc.