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Lumpuy-Castillo, JAuthorSoriano-Guillen, LAuthorLorenzo, OCorresponding Author

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Association of ACE2 Polymorphisms and Derived Haplotypes With Obesity and Hyperlipidemia in Female Spanish Adolescents

Publicated to:Front Cardiovasc Med. 9 888830- - 2022-05-02 9(), DOI: 10.3389/fcvm.2022.888830

Authors: Lumpuy-Castillo, Jairo; Vales-Villamarin, Claudia; Mahillo-Fernandez, Ignacio; Perez-Nadador, Iris; Soriano-Guillen, Leandro; Lorenzo, Oscar; Garces, Carmen

Affiliations

IIS Fdn Jimenez Diaz, Epidemiol Res Unit, Madrid, Spain - Author
Spanish Biomed Res Ctr Diabet & Associated Metab D, Madrid, Spain - Author
Univ Autonoma, Dept Pediat, IIS Fdn Jimenez Diaz, Madrid, Spain - Author
Univ Autonoma, IIS Fdn Jimenez Diaz, Lab Diabet & Vasc Pathol, Madrid, Spain - Author
Univ Autonoma, IIS Fdn Jimenez Diaz, Lipid Lab, Madrid, Spain - Author
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Abstract

BackgroundIn the cardiovascular (CV) system, overactivation of the angiotensin converting enzyme (ACE) may trigger deleterious responses derived from angiotensin (Ang)-II, which can be attenuated by stimulation of ACE2 and subsequent Ang-(1-7) metabolite. However, ACE2 exhibits a high degree of genetic polymorphism that may affect its structure and stability, interfering with these cardioprotective actions. The aim of this study was to analyse the relationship of ACE2 polymorphisms with cardiovascular risk factors in children. MethodologyFive ACE2-single nucleotide polymorphisms (SNP), rs4646188, rs2158083, rs233575, rs879922, and rs2074192, previously related to CV risk factors, were analyzed in a representative sample of 12-16-year-old children and tested for their potential association with anthropometric parameters, insulin levels and the lipid profile. ResultsGirls (N = 461) exhibited lower rates of overweight, obesity, blood pressure, and glycemia than boys (N = 412), though increased plasma lipids. The triglycerides (TG)/HDL-C ratio was, however, lower in females. Interestingly, only in girls, the occurrence of overweight/obesity was associated with the SNPs rs879922 [OR 1.67 (1.02-2.75)], rs233575 [OR 1.98 (1.21- 3.22)] and rs2158083 [OR 1.67 (1.04-2.68)]. Also, TG levels were linked to the rs879922, rs233575, and rs2158083 SNPs, and the TG/HDL-C ratio was associated with rs879922 and rs233575. Levels of TC and LDL-C were associated with rs2074192 and rs2158083. Furthermore, the established cut-off level for TG >= 90 mg/dL was related to rs879922 [OR 1.78 (1.06-2.96)], rs2158083 [OR 1.75 (1.08-2.82)], and rs233575 [OR 1.62 (1.00-2.61)]. The cut-off level for TC >= 170 mg/dL was associated with rs2074192 OR 1.54 (1.04-2.28) and rs2158083 [OR 1.53 (1.04-2.25)]. Additionally, the haplotype (C-G-C) derived from rs879922-rs2158083-rs233575 was related to higher prevalence of overweight/obesity and TG elevation. ConclusionThe expression and activity of ACE2 may be essential for CV homeostasis. Interestingly, the ACE2-SNPs rs879922, rs233575, rs2158083 and rs2074192, and the haplotype (C-G-C) of the three former could induce vulnerability to obesity and hyperlipidemia in women. Thus, these SNPs might be used as predictive biomarkers for CV diseases and as molecular targets for CV therapy.

Keywords

ace2cardiovascularhaplotypehyperlipidemiasnpAce2Blood-pressureCardiovascularCardiovascular riskEssential-hypertensionGenetic-variantsHaplotypeHyperlipidemiaInflammationObesityProteinRenin-angiotensin systemSnp

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Front Cardiovasc Med due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Cardiology and Cardiovascular Medicine.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.32, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-01, the following number of citations:

  • WoS: 3
  • Scopus: 3

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-01:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 23.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 23 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.25.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (LUMPUY CASTILLO, JAIRO) and Last Author (Garces, C).

the author responsible for correspondence tasks has been LORENZO GONZALEZ, OSCAR.