TERT and TET2 Genetic Variants Affect Leukocyte Telomere Length and Clinical Outcome in Coronary Artery Disease Patients—A Possible Link to Clonal Hematopoiesis

Inherited and acquired mutations in hematopoietic stem cells can cause clonal expansion with increased risk of cardiovascular disease (CVD), a condition known for the clonal hematopoiesis of indeterminate potential (CHIP). Inherited genetic variants in two CHIP-associated genome loci, the telomerase gene telomerase enzyme reverse transcriptase (TERT) (rs7705526) and the epigenetic regulator ten–eleven translocation 2 (TET2) (rs2454206), were investigated in 1001 patients with stable coronary artery disease (CAD) (mean age 62 years, 22% women), with regards to cardiovascular outcome, comorbidities, and leukocyte telomere length. Over 2 years, mutated TERT increased the risk two-fold for major clinical events (MACEs) in all patients (p = 0.004), acute myocardial infarction (AMI) in male patients (p = 0.011), and stroke in female patients (p < 0.001). Mutated TET2 correlated with type 2 diabetes (p < 0.001), the metabolic syndrome (p = 0.002), as well as fasting glucose, HbA1c, and shorter telomeres (p = 0.032, p = 0.003, and p = 0.016, respectively). In conclusion, our results from stable CAD patients highlight TERTs’ role in CVD, and underline TET2s’ role in the epigenetic regulation of lifestyle-related diseases

Leukocyte telomere length and serum polyunsaturated fatty acids, dietary habits, cardiovascular risk factors and features of myocardial infarction in elderly patients

Background Telomeres are non-coding sequences at the end of eukaryote chromosomes, which in complex with associated proteins serve to protect subtelomeric DNA. Telomeres shorten with each cell division, are regarded as a biomarker for aging and have also been suggested to play a role in atherosclerosis and cardiovascular disease (CVD). The aim of the present study was to explore the associations between leukocyte telomere length and serum polyunsaturated fatty acids, diet, cardiovascular risk factors and features of myocardial infarction (MI) in elderly patients. Methods The material is based upon the first 299 included patients in the OMEMI trial, where patients aged 70–82 years of age are randomized to receive omega-3 supplements or corn oil (placebo) after MI. Patients were included 2–8 weeks after the index MI. DNA was extracted from whole blood, and leukocyte telomere length (LTL) was analyzed by qPCR and reported as a number relative to a reference gene. Serum long chain polyunsaturated fatty acid (LCPUFA) content was analyzed by gas chromatography. Diet was evaluated with the validated SmartDiet food frequency questionnaire. Medical records, patient interviews and clinical examination provided previous medical history and anthropometric data. Non-parametric statistical tests were used. Results Median (25, 75 percentile) LTL was 0.55 (0.42, 0.72). Patients had a median age of 75 years, 70.2% were male and 45.2% used omega-3 supplements. There was a weak, but significant correlation between LTL and linoleic acid (r = 0.139, p = 0.017), but not with other LCPUFAs. There was a trend towards longer telomeres with a healthier diet, but this did not reach statistical significance (p = 0.073). No associations were found between LTL and CVD risk factors or features of MI. Conclusions In our population of elderly with a recent myocardial infarction LTL was associated with linoleic acid concentrations, but not with other LCPUFAs. Patients with a healthy diet tended to have longer telomeres. The limited associations may be due to age and the narrow age-span in our population. Further studies, designed to detect longitudinal changes should be performed to explore the role of telomeres in cardiovascular aging. Trial registration Clinical trials no. NCT01841944, registration date April 29, 2013

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Additional file 2: Table S2. Coefficients of correlations (r) between LTL and serum phospholipid fatty acid levels, patients with previous regular intake of n-3 supplements excluded from analysis

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Additional file 3. Methods. Description regarding CV calculations

MOESM1 of Leukocyte telomere length and serum polyunsaturated fatty acids, dietary habits, cardiovascular risk factors and features of myocardial infarction in elderly patients

Additional file 1: Table S1. Primer sequences for the telomere and single copy gene analyses

Leukocyte telomere length and serum polyunsaturated fatty acids, dietary habits, cardiovascular risk factors and features of myocardial infarction in elderly patients

Abstract Background Telomeres are non-coding sequences at the end of eukaryote chromosomes, which in complex with associated proteins serve to protect subtelomeric DNA. Telomeres shorten with each cell division, are regarded as a biomarker for aging and have also been suggested to play a role in atherosclerosis and cardiovascular disease (CVD). The aim of the present study was to explore the associations between leukocyte telomere length and serum polyunsaturated fatty acids, diet, cardiovascular risk factors and features of myocardial infarction (MI) in elderly patients. Methods The material is based upon the first 299 included patients in the OMEMI trial, where patients aged 70–82 years of age are randomized to receive omega-3 supplements or corn oil (placebo) after MI. Patients were included 2–8 weeks after the index MI. DNA was extracted from whole blood, and leukocyte telomere length (LTL) was analyzed by qPCR and reported as a number relative to a reference gene. Serum long chain polyunsaturated fatty acid (LCPUFA) content was analyzed by gas chromatography. Diet was evaluated with the validated SmartDiet food frequency questionnaire. Medical records, patient interviews and clinical examination provided previous medical history and anthropometric data. Non-parametric statistical tests were used. Results Median (25, 75 percentile) LTL was 0.55 (0.42, 0.72). Patients had a median age of 75 years, 70.2% were male and 45.2% used omega-3 supplements. There was a weak, but significant correlation between LTL and linoleic acid (r = 0.139, p = 0.017), but not with other LCPUFAs. There was a trend towards longer telomeres with a healthier diet, but this did not reach statistical significance (p = 0.073). No associations were found between LTL and CVD risk factors or features of MI. Conclusions In our population of elderly with a recent myocardial infarction LTL was associated with linoleic acid concentrations, but not with other LCPUFAs. Patients with a healthy diet tended to have longer telomeres. The limited associations may be due to age and the narrow age-span in our population. Further studies, designed to detect longitudinal changes should be performed to explore the role of telomeres in cardiovascular aging. Trial registration Clinical trials no. NCT01841944, registration date April 29, 2013

Leukocyte telomere length and serum polyunsaturated fatty acids, dietary habits, cardiovascular risk factors and features of myocardial infarction in elderly patients

Abstract Background Telomeres are non-coding sequences at the end of eukaryote chromosomes, which in complex with associated proteins serve to protect subtelomeric DNA. Telomeres shorten with each cell division, are regarded as a biomarker for aging and have also been suggested to play a role in atherosclerosis and cardiovascular disease (CVD). The aim of the present study was to explore the associations between leukocyte telomere length and serum polyunsaturated fatty acids, diet, cardiovascular risk factors and features of myocardial infarction (MI) in elderly patients. Methods The material is based upon the first 299 included patients in the OMEMI trial, where patients aged 70–82 years of age are randomized to receive omega-3 supplements or corn oil (placebo) after MI. Patients were included 2–8 weeks after the index MI. DNA was extracted from whole blood, and leukocyte telomere length (LTL) was analyzed by qPCR and reported as a number relative to a reference gene. Serum long chain polyunsaturated fatty acid (LCPUFA) content was analyzed by gas chromatography. Diet was evaluated with the validated SmartDiet food frequency questionnaire. Medical records, patient interviews and clinical examination provided previous medical history and anthropometric data. Non-parametric statistical tests were used. Results Median (25, 75 percentile) LTL was 0.55 (0.42, 0.72). Patients had a median age of 75 years, 70.2% were male and 45.2% used omega-3 supplements. There was a weak, but significant correlation between LTL and linoleic acid (r = 0.139, p = 0.017), but not with other LCPUFAs. There was a trend towards longer telomeres with a healthier diet, but this did not reach statistical significance (p = 0.073). No associations were found between LTL and CVD risk factors or features of MI. Conclusions In our population of elderly with a recent myocardial infarction LTL was associated with linoleic acid concentrations, but not with other LCPUFAs. Patients with a healthy diet tended to have longer telomeres. The limited associations may be due to age and the narrow age-span in our population. Further studies, designed to detect longitudinal changes should be performed to explore the role of telomeres in cardiovascular aging. Trial registration Clinical trials no. NCT01841944, registration date April 29, 2013