Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism and Cardiovascular Disease

Abstract

Cardiovascular disease is the major cause of morbidity and mortality in Westernised societies. It is well known that the aetiology of this devastating disorder involves both genetic and environmental factors. Sequence variants of the components of the renin-angiotensin-aldosterone system and the kallikrein-kinin system are suggested to have significant influences on cardiovascular homeostasis. Both gene targeting and transgenic studies in mice have clearly suggested a critical role of the angiotensin converting enzyme (ACE) gene in blood pressure regulation. Furthermore, an up-regulation of myocardial ACE gene expression has been observed in patients with heart failure. Thus, the ACE gene has been recognised as a top candidate gene for cardiovascular research. Over the past decade, the insertion/deletion (I/D) polymorphism of a 287-bp Alu element in intron 16 of the ACE gene has attracted significant attention and has been extensively investigated in a spectrum of cardiovascular phenotypes, because of its correlation with serum ACE activity. A large majority of previous studies have shown a positive association between the DD genotype and an increased risk of myocardial infarction, but results in hypertension, left ventricular hypertrophy, cardiomyopathy and restenosis after percutaneous transluminal coronary angioplasty remain quite controversial. Since ACE inhibitors are widely used in hypertension and congestive heart failure, we also review the literature on the relationship of ACE I/D polymorphism with ACE inhibitor response. It appears that this polymorphism has some moderate impact on the cardiovascular response to ACE inhibitors but there is no consensus as to which allele confers a more pronounced effect. In addition, previous data are suggestive of an association between the ACE I allele and a greater risk of increased occurrence of ACE inhibitor-induced cough, but such a relationship needs further confirmation. Overall, since ACE I/D is only an intronic marker, the true locus that controls the ACE enzyme activity remains to be identified, and could be located within either the ACE gene or another nearby gene such as the human growth hormone gene. We note that since associations tend to vary across different gender or ethnic groups, or across different socio-ecological settings, consideration of potential gene-gene and gene-environment interactions should be made. Furthermore, the dissection of the genetic underpinning of cardiovascular disease needs delineation of all molecular variants of the key physiological pathways that influence cardiovascular function.

Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial

“…In this study, we focused on the relationship between angiotensin-converting enzyme (ACE) gene polymorphisms (located on chromosome 17q23, consisting of 26 exons) and blood pressure response to an ACE inhibitor (ACE-I) ramipril. While some studies have begun to explore the relationship between the ACE insertion/deletion (Ins/Del) polymorphism on intron 16 and blood pressure response to ACE-Is, there is inconclusive evidence that this polymorphism results in a clinically distinct response phenotype [10]. Most studies, including the recently published Genetics of Hypertension-Associated Treatment (GenHAT) Study, compared blood pressure measurements before and after treatment initiation [11].…”

Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism

“…8,11,12,13 On the other hand, an association between the ACE I/D-polymorphism and an increased risk of myocardial infarction seems to be a rather consistent finding. 14 In order to examine systematically the role of ACE gene variants in the pathophysiology of major depression we investigated the association of 35 single-nucleotide polymorphisms (SNPs) and the ACE I/D-polymorphism within the ACE gene region covering all three ACE splice variants and the 5 0 and 3 0 neighboring genes in two ethnically homogeneous independent patient samples with major depression and two independent healthy control samples. We were then interested to investigate whether genetic variants of the ACE gene associated with unipolar major depression would also affect functional parameters such as ACE enzyme activity and HPA-axis activity.…”

Análise da tendência temporal de dano renal agudo entre pacientes graves conforme polimorfi smos I/D e -262A > T da enzima conversora da angiotensina

“…It is located in locus 17q23 and interferes in modulation of systemic vascular function, with organic repercussion of some diseases. 38,39 Many polymorphisms of ACE gene have been described, but the most frequently described in studies is the Insertion/Deletion (I/D) polymorphism. 13 It consists in the presence (allele I) or absence (allele D) of a 287 bp Alu fragment inside of the intron 16 of the ACE gene.…”