Synergistic effect of angiotensin - converting enzyme ( ACE ) & angiotensinogen gene polymorphism on the pathogenesis of acute coronary syndrome but not of chronic stable angina

Kim, Hyo Soo; Kim, Kwang Il; Chae, In Ho; Oh, Myoung Don; Sohn, Dae Won; Oh, Byung Hee; Lee, Myung Mook; Park, Young Bae; Choi, Kang Won; Choi, Yun Shik; Lee, Young Woo

Abstract

OBJECTIVES
The renin-angiotensin system(RAS) had an important role in the pathogenesis of ischemic heart disease(IHD). Angiotensinogen(ATG), angiotensin-converting enzyme(ACE), and angiotensin II receptor are key components of RAS and reported to have polymorphisms. We studied to investigate the separate and interactive effects of ACE (I/D) and ATG (M235T) gene polymorphisms on the pathogenesis of IHD, and to compare the genetic influences between on the chronic stable angina(CSA) and on the acute coronary syndrome(ACS).
METHODS
We studied total 468 patients who underwent CAG. Control group comprised 159 patients who did not have a significant coronary lesion. IHD group was subgrouped according to clinical manifestation into CSA group(n=90) and ACS group(n=219). To determine the frequency of ACE and ATG genotype, polymerase chain reaction (PCR) and enzyme digestion was done.
RESULTS
1) In ACS group, genotype frequency of ACE(II:ID:DD) was 0.27:0.48:0.25 and ATG (MM:MT:TT) was 0.31:0.59:0.10, which was significantly different from control group (ACE II:ID:DD =0.38:0.45:0.17 and ATG MM:MT:TT =0.51:0.40:0.09) (p<0.05). 2) There was no significant difference in genotype frequency of ACE, ATG gene between CSA group and control. 3) In multiple logistic regression analysis, sex, age, ATG and ACE genotype were independent risk factors for ACS. The relative risk for ACS in ACE DD compared to II genotype was 3.52 (95% CI: 1.52-8.13) and that in ACE ID compared to ACE II genotype was 1.55 (95% CI: 0.82-2.94), which showed that the risk increased with the number of ACE D-allele. In contrast, sex, age, and DM were independent risk factors for CSA, whereas ATG and ACE genotype were not. 4) In combined analysis including both ACE and ATG gene polymorphism, the relative risk for ACS associated with ATG genotype increased with the number of ACE D-allele.
CONCLUSION
ACE and ATG gene polymorphism are associated with the development of ACS but not CSA, which suggests that ACE and ATG genes may be involved in the plaque unstabilization or thrombosis rather than the chronic progression of coronary atherosclerosis.