TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model
| Autor: | Toupance, Simon, Stathopoulou, Maria, Petrelis, Alexandros, Gorenjak, Vesna, Labat, Carlos, Lai, Tsung-Po, Visvikis-Siest, Sophie, Benetos, Athanase |
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| Přispěvatelé: | Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Center of Human Development and Aging, New Jersey Medical School, Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), This work was supported by the French National Research Agency (ANR), Translationnelle: N◦ ID RCB: 2014-A00298-39: 2014-2017, the French regional project CPER-ITM2P 2015-2020, the French PIA project « Lorraine Université d’Excellence », reference ANR-15-IDEX-04-LUE and the investments for the Future program under grant agreement No. ANR-15-RHU-0004., IMPACT GEENAGE, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE (ISITE),Lorraine Université d'Excellence(2016), DE CARVALHO, Philippe, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Communication [SDV]Life Sciences [q-bio] [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system [SDV] Life Sciences [q-bio] TERC lcsh:Biology (General) cohort studies [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system atherosclerosis telomere length maintenance lcsh:QH301-705.5 [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology SNPs |
| Zdroj: | Cells Cells, MDPI, 2020, 9 (6), pp.1360. ⟨10.3390/cells9061360⟩ Cells, Vol 9, Iss 1360, p 1360 (2020) |
| ISSN: | 2073-4409 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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