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PLoS genetics2024; 20(6); e1011285; doi: 10.1371/journal.pgen.1011285

An endothelial regulatory module links blood pressure regulation with elite athletic performance.

Abstract: The control of transcription is crucial for homeostasis in mammals. A previous selective sweep analysis of horse racing performance revealed a 19.6 kb candidate regulatory region 50 kb downstream of the Endothelin3 (EDN3) gene. Here, the region was narrowed to a 5.5 kb span of 14 SNVs, with elite and sub-elite haplotypes analyzed for association to racing performance, blood pressure and plasma levels of EDN3 in Coldblooded trotters and Standardbreds. Comparative analysis of human HiCap data identified the span as an enhancer cluster active in endothelial cells, interacting with genes relevant to blood pressure regulation. Coldblooded trotters with the sub-elite haplotype had significantly higher blood pressure compared to horses with the elite performing haplotype during exercise. Alleles within the elite haplotype were part of the standing variation in pre-domestication horses, and have risen in frequency during the era of breed development and selection. These results advance our understanding of the molecular genetics of athletic performance and vascular traits in both horses and humans.
Copyright: © 2024 Fegraeus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Publication Date: 2024-06-17 PubMed ID: 38885195PubMed Central: PMC11182536DOI: 10.1371/journal.pgen.1011285Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the genetic links between blood pressure regulation and athletic performance in horses. By studying variations in the Endothelin3 (EDN3) gene, the researchers were able to correlate different gene variations with differences in blood pressure and racing performance.

Research Background and Methodology

  • The researchers built upon existing genetic studies of horse racing performance. In a prior analysis, a 19.6 kilobase (kb) regulatory region, located 50 kb downstream of the EDN3 gene, was highlighted as a factor potentially influencing performance in horses.
  • The current study further narrowed down this region to a 5.5 kb span composed of 14 single nucleotide variants (SNVs). These SNVs consist of elite and sub-elite haplotypes – groups of genes that have evolved together and are inherited as a single unit.
  • The researchers checked these haplotypes for their association to racing performance, blood pressure, and plasma levels of EDN3 in two types of horses: Coldblooded trotters and Standardbreds.

Significant Findings

  • The analysis confirmed that the 5.5 kb span acts as an enhancer cluster in endothelial cells. These are cells that line the interior surface of blood vessels and lymphatic vessels, playing a critical role in vascular biology.
  • The enhancer cluster was found to interact with genes that are important for regulating blood pressure.
  • Horses carrying the sub-elite haplotype had significantly higher blood pressure during exercise compared to those with the elite haplotype, which suggests that this gene variation could impact both blood pressure regulation and athletic performance.
  • The alleles – different forms of a gene – present in the elite haplotype were also observed in pre-domestication horses. The frequency of these alleles increased during the period of breed development and selection, indicating that they may have been favoured in the breeding of racing horses.

Implications of the Study

  • This study enhances our understanding of the genetic factors influencing athletic performance and vascular traits in both horses and, potentially, humans.
  • Deciphering the connections between blood pressure regulation and athletic performance at the genetic level can help breeders select for traits that improve racing performance in horses.
  • The findings may also have implications for human health and performance, as they offer insights into the genetics of blood pressure regulation.

Cite This Article

APA
Fegraeus K, Rosengren MK, Naboulsi R, Orlando L, Åbrink M, Jouni A, Velie BD, Raine A, Egner B, Mattsson CM, Lång K, Zhigulev A, Björck HM, Franco-Cereceda A, Eriksson P, Andersson G, Sahlén P, Meadows JRS, Lindgren G. (2024). An endothelial regulatory module links blood pressure regulation with elite athletic performance. PLoS Genet, 20(6), e1011285. https://doi.org/10.1371/journal.pgen.1011285

Publication

PLoS genetics
ISSN: 1553-7404
NlmUniqueID: 101239074
Country: United States
Language: English
Volume: 20
Issue: 6
Pages: e1011285
PII: e1011285

Researcher Affiliations

Fegraeus, Kim
  • Department of Medical Sciences, Science for life laboratory, Uppsala University, Sweden.
Rosengren, Maria K
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences Uppsala, Sweden.
Naboulsi, Rakan
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences Uppsala, Sweden.
  • Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm.
Orlando, Ludovic
  • Centre d'Anthropobiologie et de Génomique de Toulouse (CNRS UMR 5288), Université Paul Sabatier, Toulouse, France.
Åbrink, Magnus
  • Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Jouni, Ahmad
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences Uppsala, Sweden.
Velie, Brandon D
  • School of Life & Environmental Sciences, University of Sydney, Sydney, Australia.
Raine, Amanda
  • Department of Medical Sciences, Science for life laboratory, Uppsala University, Sweden.
Egner, Beate
  • Department of Cardio-Vascular Research, Veterinary Academy of Higher Learning, Babenhausen, Germany.
Mattsson, C Mikael
  • Silicon Valley Exercise Analytics (svexa), MenloPark, CA, United States of America.
Lång, Karin
  • Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden.
Zhigulev, Artemy
  • KTH Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Science for Life Laboratory, Stockholm, Sweden.
Björck, Hanna M
  • Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden.
Franco-Cereceda, Anders
  • Section of Cardiothoracic Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Eriksson, Per
  • Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden.
Andersson, Göran
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences Uppsala, Sweden.
Sahlén, Pelin
  • KTH Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Science for Life Laboratory, Stockholm, Sweden.
Meadows, Jennifer R S
  • Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Lindgren, Gabriella
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences Uppsala, Sweden.
  • Center for Animal Breeding and Genetics, Department of Biosystems, KU Leuven, Leuven, Belgium.

MeSH Terms

  • Horses / genetics
  • Animals
  • Humans
  • Blood Pressure / genetics
  • Athletic Performance / physiology
  • Haplotypes / genetics
  • Endothelin-3 / genetics
  • Polymorphism, Single Nucleotide
  • Alleles
  • Male
  • Endothelial Cells / metabolism

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 1 times.
  1. Sigurðardóttir H, Ablondi M, Kristjansson T, Lindgren G, Eriksson S. Genetic diversity and signatures of selection in Icelandic horses and Exmoor ponies. BMC Genomics 2024 Aug 8;25(1):772.
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