Abstract 524: The Interaction of Agt Gene Polymorphism with Cardiovascular Risk Traits in Atherosclerosis

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Angiotensinogen (AGT) is an important component of the renin-angiotensin system which is involved in the regulation of systemic blood pressure and many other cardiovascular functions. In the present study, we evaluated possible interaction of the AGT gene polymorphism with cardiovascular risk traits in triggering atherosclerosis in 4525 angiographed candidates, including 3232 coronary artery disease (CAD) and 2292 non-CAD individuals. Association studies were performed for 8 SNPs by the Applied Biosystems real-time PCR system. Four of the studied variants, i.e. recessive TT of rs699C>T [Odds ratio(95% Confidence Interval) = 1.29(1.16-1.43); p<0.00001], combined CT+TT of rs2148582C>T [1.28(1.08-1.52); p=0.004], AG+GG of rs5051A>G [1.30(1.09-1.55); p=0.003] and AG+GG [1.44(1.16-1.77); p=0.001] of rs2067853C>T conferred risk for primary hypertension (HTN; 3521 cases versus 1094) as well as CAD. Interestingly, the rs699 was also causative for hypercholesterolaemia [1.15(1.05-1.28); p<0.0002] and hypertriglyceridaemia 1.22(1.11-1.35); p<0.00001]. In contrast, the rs2148582 [0.90(0.82-0.980; p=0.012] and rs5051 [0.89(0.82-0.98); 0.011] showed some protective properties against acquiring type 2 diabetes mellitus (T2DM; 2544 cases versus 2070 controls), while the rs3789679 appeared be protective against HTN (0.0001) but causative for T2DM. Several haplotypes constructed from the 8 studied SNPs were either independently associated, or shared by some of the traits among themselves or with CAD. Important ones include two 8-mers GTGGGTGG (χ 2 =6.97; p=0.0083) and GTAGGCGG (χ 2 =5.69; p=0.017) associated with HTN, ACGAGTAT (χ 2 =6.76; p=0.0093) and ACGGATAT (χ 2 =9.83; p=0.0017) associated with T2DM, GTAGGCGG (χ 2 =9.43; p=0.0021) associated with obesity, and ACGGATAT (χ 2 =6.56; p=0.0104) associated with hyperlipidaemia. Put together, the data shows that AGT causative variants are partly shared among cardiovascular risk traits and CAD, pointing to the likelihood of gene-disease interaction as important contributing factor in atherosclerosis disease pathways.