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TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model

Short leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ASCVD). Mendelian randomisation studies, using single nucleotide polymorphisms (SNPs) associated with short LTL, infer a causal role of LTL in ASCVD. Recent results, using the blood-and-muscle model, ind...

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Autores principales: Toupance, Simon, Stathopoulou, Maria G., Petrelis, Alexandros M., Gorenjak, Vesna, Labat, Carlos, Lai, Tsung-Po, Visvikis-Siest, Sophie, Benetos, Athanase
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349705/
https://www.ncbi.nlm.nih.gov/pubmed/32486379
http://dx.doi.org/10.3390/cells9061360
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author Toupance, Simon
Stathopoulou, Maria G.
Petrelis, Alexandros M.
Gorenjak, Vesna
Labat, Carlos
Lai, Tsung-Po
Visvikis-Siest, Sophie
Benetos, Athanase
author_facet Toupance, Simon
Stathopoulou, Maria G.
Petrelis, Alexandros M.
Gorenjak, Vesna
Labat, Carlos
Lai, Tsung-Po
Visvikis-Siest, Sophie
Benetos, Athanase
author_sort Toupance, Simon
collection PubMed
description Short leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ASCVD). Mendelian randomisation studies, using single nucleotide polymorphisms (SNPs) associated with short LTL, infer a causal role of LTL in ASCVD. Recent results, using the blood-and-muscle model, indicate that higher early life LTL attrition, as estimated by the ratio between LTL and skeletal muscle telomere length (MTL), rather than short LTL at conception, as estimated by MTL, should be responsible of the ASCVD-LTL connection. We combined LTL and MTL measurements and SNPs profiling in 402 individuals to determine if 15 SNPs classically described as associated with short LTL at adult age were rather responsible for higher LTL attrition during early life than for shorter LTL at birth. Two of these SNPs (rs12696304 and rs10936599) were associated with LTL in our cohort (p = 0.027 and p = 0.025, respectively). These SNPs, both located on the TERC gene, were associated with the LTL/MTL ratio (p = 0.007 and p = 0.037, respectively), but not with MTL (p = 0.78 and p = 0.32 respectively). These results suggest that SNPs located on genes coding for telomere maintenance proteins may contribute to a higher LTL attrition during the highly replicative first years of life and have an impact later on the development of ASCVD.
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spelling pubmed-73497052020-07-15 TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model Toupance, Simon Stathopoulou, Maria G. Petrelis, Alexandros M. Gorenjak, Vesna Labat, Carlos Lai, Tsung-Po Visvikis-Siest, Sophie Benetos, Athanase Cells Communication Short leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ASCVD). Mendelian randomisation studies, using single nucleotide polymorphisms (SNPs) associated with short LTL, infer a causal role of LTL in ASCVD. Recent results, using the blood-and-muscle model, indicate that higher early life LTL attrition, as estimated by the ratio between LTL and skeletal muscle telomere length (MTL), rather than short LTL at conception, as estimated by MTL, should be responsible of the ASCVD-LTL connection. We combined LTL and MTL measurements and SNPs profiling in 402 individuals to determine if 15 SNPs classically described as associated with short LTL at adult age were rather responsible for higher LTL attrition during early life than for shorter LTL at birth. Two of these SNPs (rs12696304 and rs10936599) were associated with LTL in our cohort (p = 0.027 and p = 0.025, respectively). These SNPs, both located on the TERC gene, were associated with the LTL/MTL ratio (p = 0.007 and p = 0.037, respectively), but not with MTL (p = 0.78 and p = 0.32 respectively). These results suggest that SNPs located on genes coding for telomere maintenance proteins may contribute to a higher LTL attrition during the highly replicative first years of life and have an impact later on the development of ASCVD. MDPI 2020-05-31 /pmc/articles/PMC7349705/ /pubmed/32486379 http://dx.doi.org/10.3390/cells9061360 Text en © 2020 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/).
spellingShingle Communication
Toupance, Simon
Stathopoulou, Maria G.
Petrelis, Alexandros M.
Gorenjak, Vesna
Labat, Carlos
Lai, Tsung-Po
Visvikis-Siest, Sophie
Benetos, Athanase
TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model
title TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model
title_full TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model
title_fullStr TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model
title_full_unstemmed TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model
title_short TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model
title_sort terc variants associated with short leukocyte telomeres: implication of higher early life leukocyte telomere attrition as assessed by the blood-and-muscle model
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349705/
https://www.ncbi.nlm.nih.gov/pubmed/32486379
http://dx.doi.org/10.3390/cells9061360
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