The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level

Abstract

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

The role of plasma angiotensin-converting enzyme and interleukin-6 levels on the prognosis of non-dialysis chronic kidney disease patients

“…Other research, however, has not shown a correlation between circulating ACE activity and age (Miura et al, 1984;Soler et al, 2012;Yang et al, 2017). Aside from the evidence that ACE I/D polymorphism can directly affect higher ACE concentrations in plasma (Dai et al, 2019;Susilo et al, 2022), we surmise that the incongruences seen in this study may be attributable to the effect of RAAS inhibition on circulating ACE levels. In addition, different sample characteristics may potentially contribute to this discrepancy, as the majority of CKD patients in the present study have diabetes and hypertension.…”

The Role of Plasma Interleukin-6 Levels on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk Scores in Javanese Patients with Chronic Kidney Disease

“…This was an observational analytical study with a cross-sectional design to analyze the role of IL-6 G174C gene polymorphism and IL-6 plasma levels with atherosclerotic cardiovascular disease and cardiovascular mortality risk scores in Javanese CKD patients. The study is a continuation of our previous study focusing on the effect of polymorphism in the ACE gene on atherosclerotic cardiovascular disease and cardiovascular mortality risk [ 31 ]. We have added several CKD patients to be included in the present study.…”

“…The inclusion criteria were described in our previous paper [ 31 ]. Briefly, samples included in this study should fulfill the following inclusion criteria: (1) aged 40–79 years; (2) clinically stable CKD patients; and (3) Javanese ethnicity.…”

Analysis of Genes Involved in Oxidative Stress and Iron Metabolism in Heart Failure: A Step Forward in Risk Stratification

“…In this study, we focused on the I/D polymorphism. The analysis of this polymorphism (the presence of the larger insertion (I) allele or the shorter deletion (D) allele) showed that the alleles are codominant and impact the levels of plasmatic ACE with homozygotes for the I allele having the lowest levels of the enzyme, heterozygous individuals having an intermediate level and homozygotes for the D allele having the highest levels [ 11 ].…”