Development of a high-resolution melting genotyping assay for the angiotensin I converting enzyme insertion/deletion polymorphism and establishment of genotype-specific reference intervals in a Danish population

Abstract

We have developed a simple and robust method for ACE genotyping and determined genotype-specific reference intervals for s-ACE concentrations in the Danish population. The new reference intervals may increase the value of s-ACE measurements.

Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease

“…Herein, we provide evidence supporting the higher prevalence of DD genotype/D carriers of ACE I/D polymorphism in HF due to Chagas disease in a case-control study of a population from Northeast Brazil. It has been suggested that the DD genotype is associated with higher serum angiotensin (s-ACE) activity and, consequently, the conversion of angiotensin I to angiotensin II in different populations 22,23 . The genotype/phenotype correlation has been consistently associated with inflammation and tissue injury that, in turn, regulates cardiovascular risks, such as stroke or inflammatory diseases [19][20][21][22][23] .…”

“…It has been suggested that the DD genotype is associated with higher serum angiotensin (s-ACE) activity and, consequently, the conversion of angiotensin I to angiotensin II in different populations 22,23 . The genotype/phenotype correlation has been consistently associated with inflammation and tissue injury that, in turn, regulates cardiovascular risks, such as stroke or inflammatory diseases [19][20][21][22][23] . Although our cohort comprises a small number of patients in each stage and our study lacks a confirmatory functional analysis, the results are consistent and report an increased frequency of DD genotype among stage C patients compared with stages A or B1 patients.…”

“…Although our cohort comprises a small number of patients in each stage and our study lacks a confirmatory functional analysis, the results are consistent and report an increased frequency of DD genotype among stage C patients compared with stages A or B1 patients. Intronic D/I ACE polymorphism has been an important tag to the region, and several other single nucleotide polymorphisms in coding and promoter regions are in linkage disequilibrium, which might explain the functional association of this polymorphism with s-ACE activity levels 22,23,32 . The population analyzed in our study has social and economic characteristics common to most of the populations afflicted with CD, a neglected tropical disease associated with poverty 2 .…”

“…The most studied polymorphism of ACE corresponds to an insertion (I)/deletion (D) of 287 base pairs (bp) located in intron 16 and variants known as DD, ID, and II have been associated with plasma ACE activity 18 . The DD genotype, in particular, is associated with high ACE activity 22,23 , which is also related to the increased activity of angiotensin II, a key player in the pathophysiology of HF 24,25 and heart fibrosis 26 . ACE inhibitors have demonstrated efficacy in the treatment of CD 27 .…”

A Novel PCR Method for Detecting ACE Gene Insertion/Deletion Polymorphisms and Its Clinical Application

“…Rigat et al were the rst to describe a method for the detection of I/D polymorphisms using polymerase chain reaction (PCR) and agarose gel electrophoresis [1,2]. Other techniques including real-time polymerase chain reaction (RT-PCR) [3][4][5], high resolution melting (HRM) [6,5], polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) [7] and microchip electrophoresis (ME) system [8] have also been used to detect I/D polymorphism. However, these techniques require tedious experimental procedures and expensive and sophisticated instruments that may not be available in clinical institutions.…”