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      Association between angiotensin converting enzyme gene polymorphism and essential hypertension: A systematic review and meta-analysis

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          Abstract

          Background:

          The current meta-analytic study explored the relation between ACE gene insertion/deletion (I/D), and the risk of EH by reviewing relevant trials so as to determine the association between Angiotensin Converting Enzyme (ACE) gene polymorphism and essential hypertension (EH) susceptibility.

          Methods:

          Relevant studies published before May 2019 were collected from the PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases.

          Results:

          Fifty-seven studies involving a total of 32,862 patients were included. These studies found that ACE gene D allele was associated with higher EH susceptibility in allelic model, homozygote model, dominant model, and regressive model, and that Asian population with ACE gene D allele showed a higher EH susceptibility in all these models. Moreover, ACE gene D allele was found closely related to a higher EH susceptibility in the subgroups of HWE, NO HWE, Caucasian population, and Mixed population, with the majority being males in allelic model, homozygote model, and regressive model and the majority being females in allelic model.

          Conclusion:

          ACE gene D allele is associated with an overall higher EH susceptibility, which is confirmed in the subgroup analysis of Asian population, HWE, NO HWE, Caucasian population, and Mixed population.

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          Most cited references62

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          A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase.

          A novel human zinc metalloprotease that has considerable homology to human angiotensin-converting enzyme (ACE) (40% identity and 61% similarity) has been identified. This metalloprotease (angiotensin-converting enzyme homolog (ACEH)) contains a single HEXXH zinc-binding domain and conserves other critical residues typical of the ACE family. The predicted protein sequence consists of 805 amino acids, including a potential 17-amino acid N-terminal signal peptide sequence and a putative C-terminal membrane anchor. Expression in Chinese hamster ovary cells of a soluble, truncated form of ACEH, lacking the transmembrane and cytosolic domains, produces a glycoprotein of 120 kDa, which is able to cleave angiotensin I and angiotensin II but not bradykinin or Hip-His-Leu. In the hydrolysis of the angiotensins, ACEH functions exclusively as a carboxypeptidase. ACEH activity is inhibited by EDTA but not by classical ACE inhibitors such as captopril, lisinopril, or enalaprilat. Identification of the genomic sequence of ACEH has shown that the ACEH gene contains 18 exons, of which several have considerable size similarity with the first 17 exons of human ACE. The gene maps to chromosomal location Xp22. Northern blotting analysis has shown that the ACEH mRNA transcript is approximately 3. 4 kilobase pairs and is most highly expressed in testis, kidney, and heart. This is the first report of a mammalian homolog of ACE and has implications for our understanding of cardiovascular and renal function.
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            Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of Captopril in women.

            ACE2 appears to counterbalance the vasopressor effect of angiotensin I converting enzyme (ACE) in the reninangiotensin system. We hypothesized that ACE2 polymorphisms could confer a high risk of hypertension and have an impact on the antihypertensive response to ACE inhibitors. The hypothesis was tested in two casecontrol studies and a clinical trial of 3,408 untreated hypertensive patients randomized to Atenolol, Hydrochlorothiazide, Captopril, or Nifedipine treatments for 4 weeks. ACE2 rs2106809 T allele was found to confer a 1.6-fold risk for hypertension in women (95% confidence interval (CI), 1.132.06), whereas when combined with the effect of the ACE DD genotype, the risk was 2.34-fold (95% CI, 1.754.85) in two independent samples. The adjusted diastolic blood pressure response to Captopril was 3.3 mm Hg lower in ACE2 T allele carriers than in CC genotype carriers (P=0.019) in women. We conclude that the ACE2 T allele confers a high risk for hypertension and reduced antihypertensive response to ACE inhibitors.
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              Association of ACE, ACE2 and UTS2 polymorphisms with essential hypertension in Han and Dongxiang populations from north-western China.

              To assess the significance of polymorphisms of the genes for angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2) and urotensin II (UTS2) as risk factors for essential hypertension in two populations from north-western China, we enrolled 198 patients with essential hypertension and 131 healthy controls from the Han population and 120 patients with essential hypertension and 102 healthy controls from the Dongxiang population. Polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism were used to analyse gene polymorphisms. The results provided evidence that genetic variants of UTS2 and ACE2 may play a role in the development of essential hypertension in these populations. Polymorphisms of ACE were not associated with essential hypertension in either population. This is the first report showing that the S89N single-nucleotide polymorphism of the UTS2 gene is associated with essential hypertension.
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                Author and article information

                Journal
                J Renin Angiotensin Aldosterone Syst
                J Renin Angiotensin Aldosterone Syst
                JRA
                spjra
                Journal of the Renin-Angiotensin-Aldosterone System: JRAAS
                SAGE Publications (Sage UK: London, England )
                1470-3203
                1752-8976
                16 March 2021
                Jan-Dec 2021
                : 22
                : 1
                : 1470320321995074
                Affiliations
                [1 ]Ninth Hospital of Wuhan, Wuhan City, Hubei Province, China
                [2 ]Department of Endocrinology, Ninth Hospital of Wuhan, Wuhan City, Hubei Province, China
                [3 ]Department of Cardiology, Ninth Hospital of Wuhan, Wuhan City, Hubei Province, China
                Author notes
                [*]Mingyu Liu, Ninth Hospital of Wuhan, No. 20, Jilin Street, Qingshan District, Wuhan City, Hubei Province 430081, China. Email: mingyul_liumy@ 123456163.com
                Author information
                https://orcid.org/0000-0001-5317-052X
                Article
                10.1177_1470320321995074
                10.1177/1470320321995074
                7983243
                33726555
                dd2d423f-88b5-4cd8-8013-e669798af5ee
                © The Author(s) 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 30 August 2019
                : 21 January 2021
                Categories
                Original Article
                Custom metadata
                January-December 2021
                ts1

                angiotensin converting enzyme,gene polymorphism,essential hypertension,meta-analysis

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