Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents.
Author(s): Celec P, Janovičová Ľ, Gurecká R, Koborová I, Gardlík R, Sebekova K
Publication: Physiol Genomics, 2021, Vol. , Page
PubMed ID: 34097532 PubMed Review Paper? No
Purpose of Paper
The purpose of this paper was to compare total extracellular DNA (ecDNA) concentrations and mitochondrial ecDNA (mtDNA) and nuclear ecDNA (nuDNA) concentrations in plasma obtained from male and female healthy adolescents and investigate the association with blood cell counts, anthropometric data, blood pressure (BP), and levels of clinical chemistry analytes.
Conclusion of Paper
Males had higher average weight-to-height ratio, systolic BP, diastolic BP, metabolic syndrome score, and levels of uric acid, glucose, triacylglycerols, and advanced oxidation protein products; more erythrocytes; and lower insulin, high density lipoprotein cholesterol (HDL-C), non-HDL-C, and leukocyte counts than females. Consequently, males were more likely to have elevated fasting glucose, high systolic BP, high uric acid, or metabolic syndrome but males were less likely to have low HDL-C than females. Males had higher concentrations of ecDNA, mtDNA, and nDNA in their plasma than females. Weak-to-modest correlations were observed between ecDNA and nuDNA and mtDNA concentrations. ecDNA concentrations were also weakly correlated with metabolic syndrome score as well as levels of HDL-C, non-HDL-C, triacylglycerols, C-reactive protein (CRP), and advanced oxidation protein products and leukocyte erythrocyte counts but significance depended on patient gender. nuDNA concentration was correlated with HDL-C concentrations in males and erythrocyte and leukocyte counts in females. mtDNA concentration was correlated with metabolic syndrome score and levels of HDL-C, triacylglycerols, and advanced oxidation protein products concentration in males but only metabolic syndrome score in females. The authors multivariate regression model indicated associations between concentrations of ecDNA, nuDNA, or mtDNA and metabolic syndrome score, levels of advanced oxidation protein products, leukocyte counts, non-HDL-C concentrations, HDL-C, triacylglycerols, weight-to-height ratio, estimated glomerular filtration rate (eGFR), uric acid levels, CRP levels, or erythrocyte counts but strength depended on model used, patient gender, and DNA source.
Studies
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Study Purpose
The purpose of this study was to compare total ecDNA, mtDNA, and nuclear nuDNA concentration in plasma obtained from male and female healthy adolescents and investigate the association with blood cell counts, anthropometric data, blood pressure, and levels of clinical chemistry analytes. Retrospective plasma specimens from 1249 subjects (550 males aged 11-24 years and 699 females aged 11-21 years) were selected from a study evaluating cardiometabolic health status in students attending secondary schools in Bratislava based on the availability of sufficient plasma for ecDNA isolation. Patient height, waist circumference, and body weight were measured and blood pressure (BP) measured on the dominant arm after the patient had been seated for 10 min. Blood was collected between 7:00 and 9:00 in the morning after overnight fast and levels of glucose, triacylglycerols (TAG), total and high-density lipoprotein cholesterol 139 (HDL-C), uric acid, insulin, creatinine, and high-sensitive C-reactive protein (hsCRP) were measured using an autoanalyzer in a central laboratory. Heparin plasma was obtained by centrifugation at 1600 x g for 10 min followed by 6000 x g for 10 min at 4°C and stored at -80°C. ecDNA was isolated from plasma using a QIAamp 96 DNA Blood Kit and quantified by AccuBlue High Sensitivity dsDNA Quantitation Kit. ncDNA and mtDNA were quantified by real-time PCR amplification of beta-globin and D-loop, respectively. Patients were classified based on presence of obesity (weight-to-height ratio of >0.5), elevated BP (systolic BP≥130 mm Hg or diastolic BP≥85 mm Hg), elevated fasting glucose (≥5.6 mmol/L), elevated fasting insulin (≥20 μI/mL), elevated TAG (≥1.7 mmol/L, low HDL-C (<1.03 mmol/L for males and <1.29 mmol/L for females), elevated uric acid (≥420 mmol/L for males or ≥340 mmol/L for females), and elevated CRP (>3 mg/L). Metabolic syndrome was classified as presence of ≥3 of the following: elevated BP, WHtR, plasma glucose, TAG, and low HDL-C concentrations).
Summary of Findings:
Males had higher weight-to-height ratio (WHtR, P=0.001), systolic BP (P<0.001), diastolic BP (P<0.001), metabolic syndrome score (P<0.001), and levels of uric acid (P<0.001), glucose (P<0.001), triacylglycerols (P<0.001), and advanced oxidation protein products (P=0.024); more erythrocytes (P<0.001); and lower insulin (P<0.001), HDL-C(P<0.001), non-HDL-C (P<0.001), and leukocyte counts (P<0.001) than females. Further, males were more likely to have elevated fasting glucose (4.7% versus 2.1%, P=0.009), high systolic BP (22.0% versus 1.4%, P<0.001), high BP (systolic or diastolic, 23.3% versus 5.0%, P<0.001), high uric acid (12.2% versus 5.9%, P<0.001), or metabolic syndrome (12.2% versus 5.9%, P<0.001), but males were less likely to have low HDL-C (14.5% versus 21.5%, P=0.001) than females. Males had higher concentrations of ecDNA, mtDNA, and nDNA in their plasma than females (P<0.001, P<0.001, and P=0.03, respectively). Modest correlations were observed between ecDNA and nuDNA concentrations (ρ=0.529, P<0.001 for males and ρ=0.437, P<0.001 for females) and ecDNA and mtDNA concentrations were weakly correlated (ρ=0.188, P<0.001 for males and ρ= 0.241, P<0.001 for females). ecDNA concentrations were also weakly correlated with metabolic syndrome score (ρ=0.158, P<0.001 in males and ρ=0.134, P<0.001 in females), HDL-C (ρ=-0.126, P=0.003 in males and ρ= -0.118, P=0.002 in females), non-HDL-C (ρ=0.099, P=0.021 in males, not significant in females), triacylglycerols (ρ=0.141, P=0.001 in males, not significant in females), CRP (ρ=0.109, P=0.011 in males and ρ=0.078, P=0.041 in females), advanced oxidation protein products (ρ=0.202, P<0.001 in males and ρ=0.186, P<0.001 in females), leukocyte count (ρ=0.155, P<0.001 in males and ρ= 0.096, p=0.014 in females), and erythrocyte count (not significant in males, ρ=0.082, P=0.036 in females). nuDNA concentration was correlated with HDL-C concentrations (ρ=-0.095, P=0.030) in males and erythrocyte and leukocyte counts in females (ρ=0.092, p=0.024 and ρ=0.083, P=0.041, respectively). mtDNA concentration was correlated with metabolic syndrome score (ρ=0.114, P=0.011), HDL-C (ρ=-0.127, P=0.004), triacylglycerols (ρ=0.108, P=0.016), and advanced oxidation protein products concentration (ρ=0.121, P=0.007) in males, but only metabolic syndrome score in females (ρ=0.078, P=0.049). The authors multivariate regression model indicated associations between concentrations of ecDNA, nuDNA, or mtDNA and metabolic syndrome score, levels of advanced oxidation protein products, leukocyte counts, non-HDL-C concentrations, HDL-C, triacylglycerols, weight-to-height ratio, eGFR, uric acid levels, CRP levels, or erythrocyte counts but strength depended on model used, patient gender, and DNA source.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Normal
- Obesity
Platform:
Analyte Technology Platform DNA Fluorometry DNA Real-time qPCR Protein Clinical chemistry/auto analyzer Steroid Clinical chemistry/auto analyzer Carbohydrate Clinical chemistry/auto analyzer Cell count/volume Hematology/ auto analyzer Lipid Clinical chemistry/auto analyzer Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Patient gender Female
Male
Preaquisition Diagnosis/ patient condition Healthy
High blood pressure
Elevated fasting glucose
Elevated fasting insulin
Elevated triacylglycerols
Low HDL-C
Elevated CRP
Metabolic syndrome
Elevated uric acid
Real-time qPCR Specific Targeted nucleic acid Beta-globin (nuDNA)
D-loop (mtDNA)