Associations of ACE I/D polymorphism with the levels of ACE, kallikrein, angiotensin II and interleukin-6 in STEMI patients

Shuhong Dai,Shuhong Dai,Na Liang,Zhuo Li,Daqing Li,Mei Ding,Mei Ding,Lianyue Guan,Hongyu Liu,Hongyu Liu

doi:10.1038/s41598-019-56263-8

Abstract

This study aimed to compare the plasma levels of angiotensin-I converting enzyme (ACE), Angiotensin II (AngII), kallikrein (KLK1) and interleukin-6 (IL-6) in ST segment elevation myocardial infarction (STEMI) patients with different ACE Insertion/deletion (I/D) polymorphisms in a Chinese population. The ACE genotypes were determined in the 199 STEMI patients and 216 control subjects. STEMI patients were divided into three groups based on the ACE genotypes. Single polymerase chain reaction (PCR) was performed to characterize ACE I/D polymorphisms. Plasma levels of ACE, AngII, KLK1 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). We found that the DD or ID genotype was significantly independently associated with high ACE (OR = 4.697; 95% CI = 1.927–11.339), KLK1 (3.339; 1.383–8.063) and IL-6 levels (OR = 2.10; 1.025–4.327) in STEMI patients. However, there was no statistical significance between the ACE I/D polymorphism and AngII plasma levels whether in univariate or multivariate logistic regression. Additionally, we detected a significantly positive correlation between plasma KLK1 levels and IL-6 levels in STEMI patients (r = 0.584, P < 0.001). The study showed high levels of ACE, KLK1 and IL-6 were detected when the D allele was present, but AngII plasma levels was not influenced by the ACE I/D polymorphism.

Highlights

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide, and it has been estimated that approximately 50% to 60% of the major risk factors for CAD and AMI are determined by heritability[1]
Animal models and clinical studies demonstrated that angiotensin-I converting enzyme (ACE), Angiotensin II (AngII), KLK1 and IL-6 were highly expressed in unstable plaques and were significantly increased in ACS patients[10,11]
We hypothesized that changes in ACE activity through the ACE I/D polymorphism may result in an increase in vasoactive members associated with the rein-angiotensin system (RAs), Kallikrein-Kinin system (KKs) and inflammation, such as AngII, KLK1 and IL-6

Summary

Introduction

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide, and it has been estimated that approximately 50% to 60% of the major risk factors for CAD and AMI are determined by heritability[1]. Kallikrein (KLK1), which is responsible for the generation of BK, stimulated the proinflammatory cytokines IL-6 and IL-8, as another novel action of its contribution to neovascularization[7,8] Both inflammation and neovascularization have been reported to enhance plaque vulnerability[9]. Previous studies have shown interactions between RAs, KKs and inflammation[12,13] In this context, we hypothesized that changes in ACE activity through the ACE I/D polymorphism may result in an increase in vasoactive members associated with the RAs, KKs and inflammation, such as AngII, KLK1 and IL-6. The aim of the present study was to determine the possible interplay between the ACE I/D polymorphism and the important vasoactive substance of the RAs ACE, AngII, the important regulator of the KKs KLK1, and the inflammatory mediator IL-6 in patients with STEMI in the Chinese population

Objectives

Methods

Results

Conclusion