ACE 和 ACE2 活性及多态性评估：在 COVID-19 大流行期间对 Ipaussu（巴西 SP）进行的一项人口研究。

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2024-10-20 DOI:10.1016/j.lfs.2024.123157

Lilian dos Santos , Lys Angela Favaroni Mendes Salgado Ribeiro , Andréia Cristina Febba Gomes , Nayara Azinheira Nobrega Cruz , Lilian Caroline Gonçalves de Oliveira, Marcos Antonio Cenedeze, Hélio Tedesco Silva Junior, José Osmar Medina Pestana, Dulce Elena Casarini

{"title":"ACE 和 ACE2 活性及多态性评估：在 COVID-19 大流行期间对 Ipaussu（巴西 SP）进行的一项人口研究。","authors":"Lilian dos Santos , Lys Angela Favaroni Mendes Salgado Ribeiro , Andréia Cristina Febba Gomes , Nayara Azinheira Nobrega Cruz , Lilian Caroline Gonçalves de Oliveira, Marcos Antonio Cenedeze, Hélio Tedesco Silva Junior, José Osmar Medina Pestana, Dulce Elena Casarini","doi":"10.1016/j.lfs.2024.123157","DOIUrl":null,"url":null,"abstract":"<div><h3>Aim</h3><div>The angiotensin-converting enzyme 2 (ACE2) and its homolog, the angiotensin converting enzyme 1 (ACE), are involved in COVID-19 physiopathology. Alterations in the enzymatic structure, expression, and/or activity may influence the risk of infection and severity of disease. For this reason, we aimed to identify different allelic forms of <em>ACE2</em> G8790A and <em>ACE</em> I/D polymorphisms in a Brazilian cohort and evaluate their impact on ACE and ACE2 activities and their association with COVID-19 susceptibility and severity.</div></div><div><h3>Main methods</h3><div>A total of 549 COVID-19-negative and 270 COVID-19-positive participants from Ipaussu, Sao Paulo, Brazil, were recruited. ACE2 and ACE activities were measured by fluorogenic assays using MCA-Ala-Pro-Lys(Dnp) as the substrate for ACE2 and <em>Z</em>-Phe-His-Leu-OH (Z-FHL) and Hippuryl-His-Leu-OH (<em>h</em>−HL) as substrates for ACE. Genomic DNA was extracted from EDTA-peripheral blood, and the regions of the genes containing <em>ACE2</em> G8790A and <em>ACE</em> I/D polymorphisms were amplified by PCR-restriction fragment length polymorphism and real-time PCR, respectively.</div></div><div><h3>Key findings</h3><div>The G allele of <em>ACE2</em> G8790A polymorphism and D allele of <em>ACE</em> I/D polymorphism are associated with increased ACE and ACE2 activities. ACE activity ratio (<em>Z</em>-FHL/h-HL), an inflammatory marker, is increased in women with GG genotype and COVID-19-positive diagnosis.</div></div><div><h3>Significance</h3><div>For the first time, it was demonstrated that in females, the GG genotype is associated with increased ACE activity ratio (<em>Z</em>-FHL/h-HL) in the COVID-19-positive group. Elevated ACE activity ratio (Z-FHL/h-HL) is highly linked to inflammation and may justify the associations between the G genotype and COVID-19 severity of symptoms and outcomes.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123157"},"PeriodicalIF":5.2000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ACE and ACE2 activities and polymorphisms assessment: A populational study from Ipaussu (SP, Brazil) during the COVID-19 pandemic\",\"authors\":\"Lilian dos Santos , Lys Angela Favaroni Mendes Salgado Ribeiro , Andréia Cristina Febba Gomes , Nayara Azinheira Nobrega Cruz , Lilian Caroline Gonçalves de Oliveira, Marcos Antonio Cenedeze, Hélio Tedesco Silva Junior, José Osmar Medina Pestana, Dulce Elena Casarini\",\"doi\":\"10.1016/j.lfs.2024.123157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aim</h3><div>The angiotensin-converting enzyme 2 (ACE2) and its homolog, the angiotensin converting enzyme 1 (ACE), are involved in COVID-19 physiopathology. Alterations in the enzymatic structure, expression, and/or activity may influence the risk of infection and severity of disease. For this reason, we aimed to identify different allelic forms of <em>ACE2</em> G8790A and <em>ACE</em> I/D polymorphisms in a Brazilian cohort and evaluate their impact on ACE and ACE2 activities and their association with COVID-19 susceptibility and severity.</div></div><div><h3>Main methods</h3><div>A total of 549 COVID-19-negative and 270 COVID-19-positive participants from Ipaussu, Sao Paulo, Brazil, were recruited. ACE2 and ACE activities were measured by fluorogenic assays using MCA-Ala-Pro-Lys(Dnp) as the substrate for ACE2 and <em>Z</em>-Phe-His-Leu-OH (Z-FHL) and Hippuryl-His-Leu-OH (<em>h</em>−HL) as substrates for ACE. Genomic DNA was extracted from EDTA-peripheral blood, and the regions of the genes containing <em>ACE2</em> G8790A and <em>ACE</em> I/D polymorphisms were amplified by PCR-restriction fragment length polymorphism and real-time PCR, respectively.</div></div><div><h3>Key findings</h3><div>The G allele of <em>ACE2</em> G8790A polymorphism and D allele of <em>ACE</em> I/D polymorphism are associated with increased ACE and ACE2 activities. ACE activity ratio (<em>Z</em>-FHL/h-HL), an inflammatory marker, is increased in women with GG genotype and COVID-19-positive diagnosis.</div></div><div><h3>Significance</h3><div>For the first time, it was demonstrated that in females, the GG genotype is associated with increased ACE activity ratio (<em>Z</em>-FHL/h-HL) in the COVID-19-positive group. Elevated ACE activity ratio (Z-FHL/h-HL) is highly linked to inflammation and may justify the associations between the G genotype and COVID-19 severity of symptoms and outcomes.</div></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":\"358 \",\"pages\":\"Article 123157\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-10-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0024320524007471\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320524007471","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

摘要

目的：血管紧张素转换酶 2（ACE2）及其同源物血管紧张素转换酶 1（ACE）参与 COVID-19 的生理病理过程。酶结构、表达和/或活性的改变可能会影响感染风险和疾病的严重程度。为此，我们旨在确定巴西队列中 ACE2 G8790A 和 ACE I/D 多态性的不同等位基因形式，并评估它们对 ACE 和 ACE2 活性的影响及其与 COVID-19 易感性和严重程度的关联：主要方法：招募了巴西圣保罗 Ipaussu 的 549 名 COVID-19 阴性参与者和 270 名 COVID-19 阳性参与者。以 MCA-Ala-Pro-Lys(Dnp) 作为 ACE2 的底物，以 Z-Phe-His-Leu-OH (Z-FHL) 和 Hippuryl-His-Leu-OH (h-HL) 作为 ACE 的底物，通过荧光测定法测量 ACE2 和 ACE 的活性。从乙二胺四乙酸（EDTA）外周血中提取基因组 DNA，并通过 PCR-限制性片段长度多态性和实时 PCR 分别扩增了含有 ACE2 G8790A 和 ACE I/D 多态性的基因区域：主要发现：ACE2 G8790A 多态性的 G 等位基因和 ACE I/D 多态性的 D 等位基因与 ACE 和 ACE2 活性增加有关。ACE活性比值（Z-FHL/h-HL）是一种炎症标志物，在GG基因型和COVID-19阳性诊断的女性中有所增加：该研究首次证明，在 COVID-19 阳性的女性群体中，GG 基因型与 ACE 活性比率（Z-FHL/h-HL）升高有关。ACE 活性比率（Z-FHL/h-HL）的升高与炎症密切相关，这可能是 G 基因型与 COVID-19 症状严重程度和结果之间存在关联的原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

ACE and ACE2 activities and polymorphisms assessment: A populational study from Ipaussu (SP, Brazil) during the COVID-19 pandemic

Aim

The angiotensin-converting enzyme 2 (ACE2) and its homolog, the angiotensin converting enzyme 1 (ACE), are involved in COVID-19 physiopathology. Alterations in the enzymatic structure, expression, and/or activity may influence the risk of infection and severity of disease. For this reason, we aimed to identify different allelic forms of ACE2 G8790A and ACE I/D polymorphisms in a Brazilian cohort and evaluate their impact on ACE and ACE2 activities and their association with COVID-19 susceptibility and severity.

Main methods

A total of 549 COVID-19-negative and 270 COVID-19-positive participants from Ipaussu, Sao Paulo, Brazil, were recruited. ACE2 and ACE activities were measured by fluorogenic assays using MCA-Ala-Pro-Lys(Dnp) as the substrate for ACE2 and Z-Phe-His-Leu-OH (Z-FHL) and Hippuryl-His-Leu-OH (h−HL) as substrates for ACE. Genomic DNA was extracted from EDTA-peripheral blood, and the regions of the genes containing ACE2 G8790A and ACE I/D polymorphisms were amplified by PCR-restriction fragment length polymorphism and real-time PCR, respectively.

Key findings

The G allele of ACE2 G8790A polymorphism and D allele of ACE I/D polymorphism are associated with increased ACE and ACE2 activities. ACE activity ratio (Z-FHL/h-HL), an inflammatory marker, is increased in women with GG genotype and COVID-19-positive diagnosis.

Significance

For the first time, it was demonstrated that in females, the GG genotype is associated with increased ACE activity ratio (Z-FHL/h-HL) in the COVID-19-positive group. Elevated ACE activity ratio (Z-FHL/h-HL) is highly linked to inflammation and may justify the associations between the G genotype and COVID-19 severity of symptoms and outcomes.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.