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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
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International audience. Short leukocyte telomere length (LTL) is associated with atherosclerotic cardiovasculardisease (ASCVD). Mendelian randomisation studies, using single nucleotide polymorphisms(SNPs) associated with short LTL, infer a causal role of LTL in ASCVD. Recent results, using theblood-and-muscle model, indicate that higher early life LTL attrition, as estimated by the ratiobetween 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 LTLand MTL measurements and SNPs profiling in 402 individuals to determine if 15 SNPs classicallydescribed as associated with short LTL at adult age were rather responsible for higher LTL attritionduring early life than for shorter LTL at birth. Two of these SNPs (rs12696304 and rs10936599) wereassociated with LTL in our cohort (p = 0.027 and p = 0.025, respectively). These SNPs, both locatedon 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 ongenes coding for telomere maintenance proteins may contribute to a higher LTL attrition during thehighly replicative first years of life and have an impact later on the development of ASCVD.
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