Leukocyte telomere length, allelic variations in related genes and risk of coronary heart disease in people with long-standing type 1 diabetes

• Published in: Cardiovascular diabetology 2022-10, Vol.21 (1), p.1-206, Article 206
• Main Authors: Sanchez, Manuel, Kannengiesser, Caroline, Hoang, Sophie, Potier, Louis, Fumeron, Frédéric, Venteclef, Nicolas, Scheen, André, Gautier, Jean-François, Hadjadj, Samy, Marre, Michel, Roussel, Ronan, Mohammedi, Kamel, Velho, Gilberto
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adaptor Proteins, Signal Transducing/genetics; Adult; Aging; Arteriosclerosis; Atherosclerosis; BICD1 protein, human; Cardiology and cardiovascular system; Cardiovascular & respiratory systems; Cardiovascular disease; Cardiovascular diseases; Chi-square test; Cohort analysis; Cohort study; Coronary artery disease; Coronary Disease/diagnosis/epidemiology/genetics; Coronary heart disease; Cytoskeletal Proteins; Cytoskeletal Proteins/genetics; Death; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1/diagnosis/epidemiology/genetics; Diabetic retinopathy; Endocrinologie, métabolisme & nutrition; Endocrinology and metabolism; Endocrinology, metabolism & nutrition; Gene amplification; Genetics; Genetics & genetic processes; Genomics; Génétique & processus génétiques; Heart attacks; Heart diseases; Human genetics; Human health and pathology; Human health sciences; Humans; Leukocyte telomere length; Leukocytes; Life Sciences; Myocardial infarction; Myocardial Infarction/complications; Prospective Studies; Risk factors; Sciences de la santé humaine; Sciences du vivant; Single-nucleotide polymorphism; Systèmes cardiovasculaire & respiratoire; Telomerase; Telomere; Telomere/genetics; Telomeres; Type 1 diabetes; Variation
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-022-01635-0

Background Type 1 diabetes is associated with accelerated vascular aging and advanced atherosclerosis resulting in increased rates of cardiovascular disease and premature death. We evaluated associations between Leukocyte telomere length (LTL), allelic variations (SNPs) in LTL-related genes and the incidence of coronary heart disease (CHD) in adults with long-standing type 1 diabetes. Methods We assessed associations of LTL, measured at baseline by RT–PCR, and of SNPs in 11 LTL-related genes with the risk of coronary heart disease (CHD: myocardial infarction or coronary revascularization) and all-cause death during follow-up in two multicenter French-Belgian prospective cohorts of people with long-standing type 1 diabetes. Results In logistic and Cox analyses, the lowest tertile of LTL distribution (short telomeres) at baseline was associated with the prevalence of myocardial infarction at baseline and with increased risk of CHD (Hazard ratio 3.14 (1.39–7.70), p = 0.005, for shorter vs longer tertile of LTL) and all-cause death (Hazard ratio 1.63 (95% CI 1.04–2.55), p = 0.03, for shorter vs combined intermediate and longer tertiles of LTL) during follow-up. Allelic variations in six genes related to telomere biology (TERC, NAF1, TERT, TNKS, MEN1 and BICD1) were also associated with the incidence of CHD during follow-up. The associations were independent of sex, age, duration of diabetes, and a range of relevant confounding factors at baseline. Conclusions Our results suggest that short LTL is an independent risk factor for CHD in people with type 1 diabetes.