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      Influence of ACE Gene I/D Polymorphism on Cardiometabolic Risk, Maximal Fat Oxidation, Cardiorespiratory Fitness, Diet and Physical Activity in Young Adults

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          Abstract

          There is controversy about the relationship between ACE I/D polymorphism and health. Seventy-four healthy adults ( n = 28 women; 22.5 ± 4.2 years) participated in this cross-sectional study aimed at determining the influence of ACE I/D polymorphism, ascertained by polymerase chain reaction, on cardiometabolic risk (i.e., waist circumference, body fat, blood pressure (BP), glucose, triglycerides, and inflammatory markers), maximal fat oxidation (MFO), cardiorespiratory fitness (maximal oxygen uptake), physical activity and diet. Our results showed differences by ACE I/D polymorphism in systolic BP (DD: 116.4 ± 11.8 mmHg; ID: 116.7 ± 6.3 mmHg; II: 109.4 ± 12.3 mmHg, p = 0.035) and body fat (DD: 27.3 ± 10.8%; ID: 22.6 ± 9.7%; II: 19.3 ± 7.1%, p = 0.030). Interestingly, a genotype*sex interaction in relativized MFO by lean mass ( p = 0.048) was found. The DD polymorphism had higher MFO values than ID/II polymorphisms in men (8.4 ± 3.0 vs. 6.5 ± 2.9 mg/kg/min), while the ID/II polymorphisms showed higher R-MFO values than DD polymorphism in women (6.6 ± 2.3 vs. 7.6 ± 2.6 mg/kg/min). In conclusion, ACE I/D polymorphism is apparently associated with adiposity and BP, where a protective effect can be attributed to the II genotype, but not with cardiorespiratory fitness, diet and physical activity. Moreover, our study highlighted that there is a sexual dimorphism in the influence of ACE I/D gene polymorphism on MFO.

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          Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019

          Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
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            Metabolic Flexibility in Health and Disease.

            Metabolic flexibility is the ability to respond or adapt to conditional changes in metabolic demand. This broad concept has been propagated to explain insulin resistance and mechanisms governing fuel selection between glucose and fatty acids, highlighting the metabolic inflexibility of obesity and type 2 diabetes. In parallel, contemporary exercise physiology research has helped to identify potential mechanisms underlying altered fuel metabolism in obesity and diabetes. Advances in "omics" technologies have further stimulated additional basic and clinical-translational research to further interrogate mechanisms for improved metabolic flexibility in skeletal muscle and adipose tissue with the goal of preventing and treating metabolic disease.
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              An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.

              A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                26 March 2021
                April 2021
                : 18
                : 7
                : 3443
                Affiliations
                [1 ]MOVE-IT Research Group, Department of Physical Education, Faculty of Education Sciences, University of Cadiz, 11519 Puerto Real, Spain; adrianmontes96@ 123456hotmail.com (A.M.-d.-O.-G.); daniel.velazquez@ 123456uca.es (D.V.-D.); juan.corral@ 123456uca.es (J.C.-P.); ed.opazodiaz@ 123456alum.uca.es (E.O.-D.); maria.rebollo.ramos@ 123456gmail.com (M.R.-R.); jesusgustavo.ponce@ 123456uca.es (J.G.P.-G.)
                [2 ]Instituto de Investigación Biomédica de Cádiz (INiBICA), Hospital Uniersitario Puerta del Mar, Universidad de Cádiz, 11009 Cádiz, Spain; alejandro.perezperez@ 123456uca.es (A.P.-B.); magdalena.cuenca@ 123456uca.es (M.C.-G.)
                [3 ]GALENO Research Group, Department of Physical Education, Faculty of Education Sciences, University of Cadiz, 11519 Puerto Real, Spain
                [4 ]Department of Physical Therapy, Faculty of Medicine, University of Chile, Independencia 1027, Santiago 8380453, Chile
                [5 ]Faculty of Health Sciences, International University of La Rioja, 26006 Logroño, Spain; 2010gmz@ 123456gmail.com
                Author notes
                [* ]Correspondence: cristina.casals@ 123456uca.es ; Tel.: +34-677-180-597
                Author information
                https://orcid.org/0000-0002-4874-5840
                https://orcid.org/0000-0002-9849-5544
                https://orcid.org/0000-0002-6574-9827
                https://orcid.org/0000-0003-0057-5333
                https://orcid.org/0000-0002-6992-0492
                https://orcid.org/0000-0002-5982-7761
                Article
                ijerph-18-03443
                10.3390/ijerph18073443
                8036598
                33810312
                b50eddc2-3180-4aef-bc12-3415d4b0a6d7
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 February 2021
                : 23 March 2021
                Categories
                Article

                Public health
                genetic association studies,heart diseases,lipid metabolism,healthy lifestyle,angiotensin-converting enzyme,obesity

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