Research Paper Volume 13, Issue 20 pp 23517—23526

A genetic determinant of VEGF-A levels is associated with telomere attrition

Vesna Gorenjak1, *,#, , Alexandros M. Petrelis1, *,#, , Maria G. Stathopoulou1, *, , Simon Toupance2, *, , Satish Kumar1, , Carlos Labat2, , Christine Masson1, , Helena Murray3, , John Lamont3, , Peter Fitzgerald3, , Athanase Benetos2,4, *, , Sophie Visvikis-Siest1, *, , TELARTA consortium ,

  • 1 Université de Lorraine, IGE-PCV, Nancy F-54000, France
  • 2 Université de Lorraine, Inserm, DCAC, Nancy F-54000, France
  • 3 Randox Laboratories Limited, Crumlin, Co. Antrim BT29 4QY, Northern Ireland, United Kingdom
  • 4 Université de Lorraine, CHRU-Nancy, Pôle “Maladies du Vieillissement, Gérontologie et Soins Palliatifs”, Nancy F-54000, France
* Equal contribution
# Co-first author

Received: March 18, 2021       Accepted: October 3, 2021       Published: October 18, 2021      

https://doi.org/10.18632/aging.203636
How to Cite

Copyright: © 2021 Gorenjak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Telomere length (TL) is a hallmark of cellular aging and is associated with chronic diseases development. The vascular endothelial growth factor A (VEGF-A), a potent angiogenesis factor, is implicated in the pathophysiology of many chronic diseases. The aim of the present study was to investigate the associations between VEGF-A and TL.

TL in leukocytes (LTL) and skeletal muscle (MTL) were measured, 10 VEGF-related polymorphisms genotyped, and VEGF-A plasma concentrations determined in 402 individuals from the TELARTA cohort. LTL/MTL ratio was calculated as an estimate of lifelong TL attrition. Associations between VEGF-A variants and levels, and TL parameters were investigated.

We identified one significant association between the minor allele (T) of rs6993770 variant and LTL/MTL ratio (P=0.001143, β=0.0148, SE=0.004516). The rs6993770 is an intronic variant of the ZFPM2 gene, which is involved in haematopoiesis and the identified association with increased telomere attrition could be due to increased haematopoiesis. No significant epistatic interaction was identified, and no association was found between levels of VEGF-A and any of assessed phenotypes.

We identified a potential common genetic regulation between VEGF-A and telomere length attrition that could be explained by mechanisms of increased hematopoiesis and production of platelets. VEGF-A and TL could play an important role in personalized medicine of chronic diseases and identification of molecular links between them can promote the understanding of their complex implications.

Abbreviations

CVD: Cardiovascular disease; CVD: Cardiovascular diseases; FDA: Food and Drug Administration; FOG: Friend of GATA; GWAS: Genome-wide association study; HDL: High-density lipoproteins; HWE: Hardy-Weinberg equilibrium; IL: Interleukin; LTL: Leukocyte telomere length; MAF: Minor allele frequency; MTL: Muscle telomere length; SE: Standard error; SNP: Single nucleotide polymorphism; TL: Telomere length; VEGF-A: Vascular endothelial growth factor A; ZFP: Zinc finger protein.